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Introduction: Pseudoaneurysm is a serious complication after pancreatic surgery, which mainly depends on the presence of a preceding pancreatic fistula. Postpancreatectomy hemorrhage following total pancreatectomy is a rare complication due to the absence of a pancreatic fistula. Here we report an unusual case of massive gastrointestinal bleeding due to right hepatic artery (RHA) pseudoaneurysm following total remnant pancreatectomy., Presentation of Case: A 75-year-old man was diagnosed with intraductal papillary mucinous carcinoma recurrence following distal pancreatectomy and underwent total remnant pancreatectomy. After discharge, he was readmitted to our hospital with melena because of the diagnosis of gastrointestinal bleeding. Gastrointestinal endoscopy was performed to detect the origin of bleeding, but an obvious bleeding point could not be detected. Abdominal computed tomography demonstrated an expansive growth, which indicated RHA pseudoaneurysm. Emergency angiography revealed gastrointestinal bleeding into the jejunum from the ruptured RHA pseudoaneurysm. Transcatheter arterial embolization was performed; subsequently, bleeding was successfully stopped for a short duration. Because of improvements in his general condition, the patient was discharged., Discussion: To date, very few cases have described postpancreatectomy hemorrhage following total remnant pancreatectomy. We suspect that the aneurysm ruptured into the jejunum, possibly because of the scarring and inflammation associated with his two complex surgeries., Conclusion: Pseudoaneurysm should be considered when the fragility of blood vessels is suspected, despite no history of anastomotic leak and intra-abdominal abscess. Our case also highlighted that detecting gastrointestinal bleeding is necessary to recognize sentinel bleeding if the origin of bleeding is undetectable.

Background: Lactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels., Methods: The study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204-259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels., Results: After 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p < 0.05) and a significantly greater decrease than for the 4 g group (3.1 ± 3.4 mg/dL; p < 0.05). Serum LDL-C levels in the 8 g group decreased by 13.7 ± 3.1 mg/dL, again a significant decrease compared with baseline (p < 0.05) and a significantly greater decrease than that for the 4 g group (2.1 ± 2.9 mg/dL; p < 0.05)., Conclusion: Consumption of LE for 8 weeks at a daily dose of 8 g of proteins reduced serum TC and LDL-C levels in men with mild hypercholesterolemia, suggesting this may be effective in helping to prevent arteriosclerotic diseases., Trial Registration: This clinical trial was retrospectively registered with the Japan Medical Association Center for Clinical Trials, (JMA-IIA00279; registered on 13/03/2017; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02&#95;04/JMACTRE02&#95;04.aspx?kbn=3&seqno=6530 ).

The egg is a nutrient-dense food and contains a number of antioxidants. The consumption of eggs has been considered to improve the balance of diets, although its impact on serum cholesterol levels has been a matter of concern in many countries. Here, we conducted a pilot study to investigate whether daily additional consumption of an egg might affect serum lipid profiles and also antioxidant status in healthy subjects. Fourteen male subjects were provided with breakfasts including a boiled egg for 4 wk. At the end of intervention, serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were unchanged, despite the significant increase in the intake of dietary cholesterol. In contrast, a significant increase in high-density lipoprotein cholesterol (HDL-C) and a reduction of the LDL-C/HDL-C ratio were observed. Interestingly, the malondialdehyde modified-LDL (MDA-LDL)/LDL-C ratio and the oxidizability of LDL were significantly reduced. Serum total antioxidant capacity value after the intervention period was higher than at baseline. These data indicate that consuming one egg per day for 4 wk as breakfast in addition to a normal diet does not affect serum lipids, and suggests that it may improve serum antioxidant status in healthy males.

Betaine uptake is induced by hypertonic stress in a placental trophoblast cell line, and involvement of amino acid transport system A was proposed. Here, we aimed to identify the subtype(s) of system A that mediates hypertonicity-induced betaine uptake. Measurement of [(14)C]betaine uptake by HEK293 cells transiently transfected with human or rat sodium-coupled neutral amino acid transporters (SNATs), SNAT1, SNAT2 and SNAT4 revealed that only human and rat SNAT2 have betaine uptake activity. The Michaelis constants (Km) of betaine uptake by human and rat SNAT2 were estimated to be 5.3 mM and 4.6 mM, respectively. Betaine exclusively inhibited the uptake activity of SNAT2 among the rat system A subtypes. We found that rat SNAT1, SNAT2 and SNAT4 were expressed at the mRNA level under isotonic conditions, while expression of SNAT2 and SNAT4 was induced by hypertonicity in TR-TBT 18d-1 cells. Western blot analyses revealed that SNAT2 expression on plasma membrane of TR-TBT 18d-1 cells was more potently induced by hypertonicity than that in total cell lysate. Immunocytochemistry confirmed the induction of SNAT2 expression in TR-TBT 18d-1 cells exposed to hypertonic conditions and indicated that SNAT2 was localized on the plasma membrane in these cells. Our results indicate that SNAT2 transports betaine, and that tonicity-sensitive SNAT2 expression may be involved in regulation of betaine concentration in placental trophoblasts., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the effects of egg white protein compared to carbohydrate intake prior to exercise on fat free mass (FFM), one repetition maximum (1RM) muscle strength and blood biochemistry in female athletes. Thirty healthy female collegiate athletes were recruited for this study and matched by sport type, body fat percentage and 1RM leg curl muscle strength. Participants were randomly divided into two groups: protein group (15.0 g egg white protein; 75 kcal) and carbohydrate group (17.5 g maltodextrin, 78 kcal). Supplements were administered daily at the same time in a double-blind manner prior to training during an 8-week period. Measurements were performed before and after the 8-week regimen. The mean dietary energy intake did not change throughout the study period. FFM and 1RM assessments (i.e., leg curl, leg extension, squat, and bench press) increased in both groups. Furthermore, serum urea and serum citrulline levels after the 8-week regimen increased significantly only in the protein group. Our findings indicated that compared to the carbohydrate supplement, the protein supplement was associated with some changes in protein metabolites but not with changes in body composition or muscle strength.

We retrospectively investigated increases in large granular lymphocytes (LGL) in peripheral blood during dasatinib treatment in 25 chronic myelogenous leukemia patients. Fifteen of 25 patients (60 %) showed an increase in LGL. All 15 of these patients also showed an increase in NK cells, and 11 showed an increase in CD8(+) T cells. High frequencies of clonal rearrangements of TCR-β, -γ, and -δ genes were observed in LGL (+) patients, and at lower frequencies in LGL (-) patients as well. Clinical responses were favorable for all. With respect to their newly obtained complete molecular response after dasatinib treatment, LGL (+) patients showed higher response rates than did LGL (-) patients. In contrast, pleural effusions were more commonly observed in LGL (+) patients (60 %) than in LGL (-) patients (20 %). LGL counts significantly increased at 2 h after oral intake of dasatinib in all 25 patients. This was not observed in treatment with imatinib or nilotinib. Cytomegalovirus (CMV) C7-HRP tests were negative in all patients. Serum CMV-IgM antibodies were positive in only 2 of 25 patients without symptom of infection. Thus, LGL lymphocytosis during dasatinib treatment may be correlated with favorable molecular response, and with increased incidence of pleural effusions. In the clinical setting, CMV reactivation appears uncommon.

To clarify the effects of different physical forms of oil on postprandial serum lutein/zeaxanthin and beta-carotene concentrations, we performed a vegetable meal loading test. Eighteen healthy subjects participated in the test, which consisted of broccoli as a control (CON) meal, broccoli with oil (OIL), and broccoli with mayonnaise (MS), consumed in random order. After collection of fasting blood samples, subjects consumed one of the three test meals. Fasting and postprandial changes in serum carotenoids were assessed 2, 4, and 6 h after ingestion of each test meal. Serum lutein/zeaxanthin and beta-carotene concentrations were measured. Although no significant change was noted after the CON meal, the serum lutein/zeaxanthin concentration was higher at 4 h after consumption of the OIL meal, and at 2, 4 and 6 h after consumption of the MS meal, as compared with the fasting state. Serum beta-carotene concentrations did not change after ingestion of either the CON or the OIL meal but were elevated 2, 4, and 6 h after MS ingestion as compared with the fasting state. The incremental areas under the curves (IAUCs) of serum lutein/zeaxanthin and beta-carotene concentrations were higher after the MS meal than after the CON meal. IAUCs after the OIL meal exhibited no statistically significant differences from the CON and MS meals. We suggest that mayonnaise contributes to increase serum lutein/zeaxanthin and beta-carotene concentrations when consumed with vegetables rich in these carotenoids.

To our knowledge, no prospective study has examined the association between blood levels of organochlorines and breast cancer risk in Asian countries. Here, we tested the hypothesis that higher blood levels of organochlorines are associated with an increased risk of breast cancer in Japanese women. A total of 24,226 women subjects of the Japan Public Health Center-based Prospective Study aged 40 to 69 years who responded to the baseline questionnaire and provided blood in 1990-1995 were followed to December 2002. During 10.7 years follow-up, 144 cases of breast cancer were newly diagnosed. Two matched-controls for each case were selected from the cohort. Plasma levels of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (beta-HCH) were measured. A conditional logistic regression was used to estimate the odds ratio (OR) of breast cancer according to cholesterol-adjusted organochlorine levels based on 139 matched pairs. We found no statistically significant positive association between plasma organochlorine level and breast cancer risk. Adjusted ORs for p,p'-DDT, HCB, and beta-HCH were less than 1. For p,p'-DDE, adjusted OR for the highest versus lowest quartile was 1.48 (95% confidence interval 0.70-3.13; p for trend=0.25). A stratified analysis by menopausal status showed positive associations for p,p'-DDT and p,p'-DDE in premenopausal but not postmenopausal women, although without statistical significance. Our data do not support the hypothesis that plasma levels of p,p'-DDT, p,p'-DDE, HCB, and beta-HCH are associated with an overall increased risk of breast cancer among Japanese women.

Aberrant expression of sialoglycoconjugates has been thought to play an important role in cancer progression. Our previous lectin-histochemical study showed that overexpression of sialoglycoconjugates recognized by alpha2,3-sialic acid-specific Maackia amurensis leukoagglutinin (MAL) was significantly related to the malignancy of gastric cancer. The present study analyzed the sialoglycoproteins in gastric cancer tissues by 2-dimensional electrophoresis (2-DE) in combination with lectin-binding analysis using MAL. Various MAL-positive sialoglycoproteins were detected in cancer tissues but not in non-cancer tissues. The sialoglycoproteins have a high molecular weight of near 200 kDa and over 200 kDa with different pI values for the two. This suggests that the MAL-positive sialoglycoproteins detected in gastric cancer tissues have high molecular weights and may contain different numbers of alpha2,3-linked sialic acid residues in the carbohydrate moiety.

Mouse embryonic stem (ES) cells can self-renew in the presence of leukemia inhibitory factor (LIF). Several essential transcription factors have been identified for the self-renewal of mouse ES cells, including STAT3, Oct-3/4, and Nanog. The molecular mechanism of ES cell self-renewal, however, is not fully understood. In the present study, we identified Eed, a core component of Polycomb repressive complex 2, as a downstream molecule of STAT3 and Oct-3/4. Artificial activation of STAT3 resulted in increased expression of Eed, whereas expression of a dominant negative mutant of STAT3 or suppression of Oct-3/4 expression led to down-regulation of Eed. Reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays revealed that STAT3 and Oct-3/4 directly bind to the promoter region of Eed, suggesting that Eed is a common target molecule of STAT3 and Oct-3/4. We also found that suppression of STAT3, Oct-3/4, or Eed causes induction of differentiation-associated genes as well as loss of Lys(27)-trimethylated histone H3 at the promoter regions of the differentiation-associated genes. Suppression of STAT3 and Oct-3/4 also resulted in the absence of Eed at the promoter regions. These results suggest that STAT3 and Oct-3/4 maintain silencing of differentiation-associated genes through up-regulation of Eed in self-renewing ES cells.

In a placebo-controlled double-blind study, we examined the effects of dressing containing plant sterol (PS) on blood lipids and the safety in Japanese borderline or mildly hypercholesterolemic subjects. Fifty-nine subjects [total cholesterol (TC) concentration > or = 200 mg/dL] were randomly divided into two groups and were given daily 15 g of dressing containing 800 mg of PS [PS(+)-group] or without PS [PS(-)-group] for 12 weeks. Every 4 weeks, fasting blood was examined and subjective symptoms were analyzed. Serum TC, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) concentrations did not change in the PS(-)-group, while TC and ApoB significantly decreased in the PS(+)-group at 8 and 12 weeks and LDL-C at 4, 8 and 12 weeks. Moreover, serum TC, LDL-C and ApoB concentrations were significantly lower than those of PS(-)-group at 8 and 12 weeks. Other laboratory tests were all in normal ranges and no adverse events were observed. The results indicated that PS-containing dressing decreased serum TC, LDL-C and ApoB concentrations in borderline or mildly hypercholesterolemic subjects. It is therefore proved that the dressing containing PS is helpful in maintaining blood cholesterol level normal and hence, the health of Japanese.

We examined the minimal effective dose on serum cholesterol concentration and the safety of dressing containing plant sterol in humans. EXP.1: Sixty-eight healthy Japanese males (total cholesterol (TC) > or = 170 mg/dL) were randomly divided into four groups, and were given 0, 400, 800 or 1200 mg/day of plant sterol in 15 g dressing for 4 weeks followed by the washout period of 4 weeks. Although there were no significant differences in serum TC and low-density lipoprotein cholesterol (LDL-C) concentrations among all groups after feeding plant sterol for 4 weeks, in 36 subjects with TC > or = 220 mg/dL, serum LDL-C concentration tended to reduce when received 800 or 1200 mg of plant sterol, and the difference between 0 and 1200 mg groups was statistically significant. The difference between 0 and 800 mg groups was near significant (p=0.053). Intake of 400 mg of plant sterol did not change serum LDL-C concentration. EXP.2: Twenty-one healthy Japanese subjects (TC > or = 180 mg/dL, 10 men, 11 women) were given 2400 mg/day of plant sterol in 45 g dressing for 4 weeks. Clinical data were all remained normal. These results indicated that minimal effective dose of the plant sterol on serum cholesterol concentration in healthy male subjects is around 800 mg/day, and intake of 2400 mg/day of plant sterol is regarded to be safe.

We have previously reported that gamma-tocopherol (gamma-Toc) displays a natriuretic potency in rats fed a NaCl diet and administered 20 mg gamma-Toc. In this study, we investigated whether gamma-Toc has natriuretic potency at a dose lower or higher than 20 mg in rats given a NaCl diet. Male rats were fed a control diet or a NaCl diet and administered either placebo or 10, 20 or 40 mg of gamma-Toc. The rat urine was collected for 24 hours (divided into 6 hour periods) and the 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) level, the sodium excretion content, and the urine volume were determined. The 24-hour gamma-CEHC and sodium levels in the urine of the NaCl groups given 20 mg or 40 mg gamma-Toc were significantly higher than those in the placebo group. The peak levels of urine sodium and gamma-CEHC in the NaCl group given 40 mg gamma-Toc appeared at 0-6 h, which was a more rapid increase than that seen in the group given 20 mg gamma-Toc. The 24-hour urine volumes of the NaCl groups given 10 and 20 mg gamma-Toc were significantly higher than the urine volume of the placebo group. Our findings suggested that gamma-Toc increased sodium excretion in a dose-dependent manner in rats fed a NaCl diet. Moreover, a high dose of gamma-Toc may accelerate its metabolism and cause an increase in the rate of sodium excretion.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal. In this study, we searched for molecules downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat binding protein (GABP) alpha. Expression of GABPalpha was restricted to undifferentiated ES cells and controlled by STAT3. We found that the expression level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand, GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4 repressors.

Background: When residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs., Methods: Fourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava., Results: In the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 +/- 3.8 mmHg in the group without a shunt and 10.5 +/- 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt., Conclusions: These results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury.

The concentrations of metabolites in human plasma after ingestion of flavanone glycosides (FG) and their aglycones (FA) in lemon were examined. FG consisting abundantly of eriocitrin were prepared from lemon peel and FA consisting abundantly of eriodictyol were prepared from FG by treatment with beta-glucosidase. Eriodictyol, homoeriodictyol, and hesperetin in plasma up to 4 h after ingestion of FG with water or FA with water by subjects were not detected in plasma of non-enzyme treatment but in plasma after treatment with beta-glucronidase and sulfatase. Metabolites in plasma after ingestion of FG and FA in humans were shown to exist as the glucuro- and/or sulfo-conjugates of eriodictyol, homoeriodictyol, and hesperetin. After ingestion of FA, the concentration of metabolites in plasma exhibited a high maximum peak at 1 h. The AUC (area under the blood concentration time curve) level of metabolites of FA was higher than that of FG. FA were suggested to be absorbed faster and in higher amounts than FG. The AUC of metabolites in subject plasma after ingestion of FG with flavonoid-depleted lemon juice was shown to change to a low level in comparison with that of FG with water. The maximum concentration peak of metabolites in plasma was faster at 0.5 h than FA with water but the AUC level was similar to FA with water, when subjects ingested FA with vodka (40%, ethanol). The absorption hour of FG and FA was shown to be affected by the co-existing solution.

Aim: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely small-for-size liver transplantation in pigs., Methods: The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated., Results: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2+/-26.9 mL/min/100 g liver tissue and 270.5+/-72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2+/-27.8 mL/min/100 g liver tissue and 42.7+/-32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt., Conclusion: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal.

Data concerning clinical cases of pesticide poisoning from 1998 to 2002 from the hospitals affiliated with the Japanese Association of Rural Medicine were analyzed. 346 cases of poisoning by agricultural chemicals were reported from 65 hospitals. Suicides accounted for 70% of pesticide poisoning cases, followed by accidental exposures during spraying work (16%) and accidental ingestion (8%). The majority of cases were acute or subacute systemic poisonings (90%), followed by acute dermatitis (5%) and chemical burns (3%). Organophosphate insecticide was the most frequent inducer of clinical cases (36%), followed by bipyridylium herbicide (20%) and carbamate insecticide (6%). The death rate from poisoning by the herbicide paraquat was more than 70% of clinical cases, even though it is a low-concentration product, whereas those from the alternative herbicides, glufosinate and glyphosate, were less than 10%.

Background: Humoral rejection after ABO-incompatible liver transplantation often causes graft loss and a life-threatening situation. We used rituximab, which can eliminate B cells highly selectively, as an additional therapy for ABO-incompatible living-related liver transplantation., Cases: Patient 1 was a 1-year-old girl with biliary atresia. Her blood type was O, and the donor's was A. She underwent two plasma exchanges before liver transplantation and had triple immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone). She was diagnosed with humoral rejection by needle biopsy on postoperative day 6. Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral blood lymphocytes. The patient has not had any severe rejection, infection, or serious complications 2 years posttransplantation. Patient 2 was a 42-year-old woman with primary biliary cirrhosis. The blood type was O, and the donor's was B. She received three plasma exchanges, triple immunosuppressants, splenectomy, intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after transplantation). The titer and CD19(+) cells count remained persistently low throughout the recovery course. She did not develop humoral rejection 1 year after transplantation., Conclusions: Rituximab efficiently reduces anti-ABO antibody titer by selectively eliminating B cells and is safe and effective against humoral rejection after ABO-incompatible liver transplantation.

Serious intestinal bleeding from vascular ectasia secondary to extrahepatic portal thrombosis is much less frequent than variceal bleeding, and its treatment is not clearly defined. We describe a 4-year-old girl with repeated intestinal bleeding from vascular ectasia, without any varix, with late extrahepatic portal vein thrombosis (PVT) and late hepatic artery thrombosis (HAT) after living-related liver transplantation. The bleeding stopped after simple splenectomy. She has presented neither bleeding nor any serious complications related to splenectomy for 1 year to date. We think uncontrollable hemorrhage from gastrointestinal vascular ectasia secondary to extrahepatic portal thrombosis in a pediatric patient can and should be treated by simple splenectomy, because patients with this complication usually have a normally functioning liver. However, it is not clear whether this procedure is effective for variceal bleeding.

Background/aims: Cell surface glycosylation changes during oncogenesis and is thought to correlate with the malignant potential of cancers. To investigate the role of sialylation in carcinoma of the papilla of Vater, histochemical analyses were performed using sialic acid-binding lectins, Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin., Methodology: Thirty-six papillary carcinoma tissues and 8 normal papillary tissues were subjected to lectin-histochemical staining. The relationship between lectin staining characteristics and clinicopathological parameters was statistically analyzed., Results: Epithelial cells of glands in normal tissues were stained with Sambucus nigra agglutinin but not with Maackia amurensis leukoagglutinin. Of 36 papillary carcinoma tissues, 20 showed Maackia amurensis leukoagglutinin-positive staining in cancer cells, whereas all 36 were Sambucus nigra agglutinin-positive in cancer cells. According to Maackia amurensis leukoagglutinin-staining characteristics, the 36 cases were divided into two groups: positive (n=20) and negative (n=16). Statistical analysis indicated that positive staining in cancer cells was frequent in cases of lymph node metastasis (p=0.001) and in cases classified > or = T2 by TNM classification (p=0.036)., Conclusions: Aberrant expression of sialoglycoconjugates recognized by Maackia amurensis leukoagglutinin might participate in lymph node metastasis and in an advanced stage of invasion in carcinoma of the papilla of Vater.

X-ray anomalous diffraction, together with a band-structure calculation, was employed to obtain a quantitative understanding of the charge-ordering state in a single-crystalline CaFeO3 thin film. The experimental result shows a characteristic energy dispersion of the nearly inhibited reflection at 150 K, implying Fe atoms split into two distinct states. The energy dispersion is in good agreement with the calculated spectrum based on the LDA+U scheme. The calculation also reveals an electronic structure of the system where holes in the oxygen orbital surround one of the distinct Fe atoms, in spite of the total electron number in both Fe atoms remaining unchanged.

In partial-liver transplantation, the use of small grafts sometimes results in graft failure, usually caused by portal hypertension after transplantation (Tx). Portal hypertension after Tx can be decreased with a porto-caval shunt (PCS). The purpose of this study is to clarify the effect of the PCS on extremely reduced-size liver Tx. In a pig model, the posterior segment of 25% of a whole liver was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS ( n=7), and group B, graft without PCS ( n=7). The PCS was made by means of side-to-side anastomosis of the portal vein and the inferior vena cava. We examined the portal vein pressure, survival rate, regeneration rate of the graft, Ki-67 as an index of cell proliferation, and histological findings, and carried out liver-function tests. In group A, five pigs survived for more than 4 days and the remaining two died of a perforated gastric ulcer on post-operative day (POD) 2. In group B, all pigs except one died of graft failure within 24 h. Portal vein pressure after reperfusion in group A and group B was of statistically significant difference ( P<0.05), 14.2+/-3.2 and 18.9+/-4.7 cmH(2)O, respectively. In group A, the regeneration rate of the graft was 94%, 4 days after Tx, and Ki-67 stained remarkably in the parenchymal hepatocytes. In TEM finding, structure of the sinusoid was also well maintained after Tx. From these results we can conclude that the key to success in liver Tx with extremely small grafts lies in the control of the portal vein pressure.

An effective way to overcome shortage of donors in liver transplantation (LTx) is to consider such from non-heart-beating donors (NHBDs). We investigated how a liver graft should be treated before and/or after procurement for successful LTx from an NHBD. Porcine LTx was performed with FR167653 (FR), a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and/or prostaglandin E(1) (PG). Animals were allocated to an FR group (n=4, donors and recipients were treated with FR), a PG group (n=4, donors and recipients were treated with PG), or an FRPG group (n=4, donors and recipients were treated with both FR and PG). No recipients in the FR group and only two of four recipients in the PG group survived, whereas all recipients in the FRPG group survived. Suppression of TNF-alpha and IL-1beta and maintenance of microcirculation are the key to successful transplantation from NHBDs.

Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.

In order to evaluate the effects of the rapid induction and the slow induction of general anesthesia on the management of anesthesia and the circadian rhythm, the time-dependent whole body heat production in mice (ICR, male, 6 to 10 weeks after birth) was measured by calorimeter. In the single administration of either an i.v. anesthetic (thiamylal) or a volatile anesthetic (isoflurane), the minimum heat production and its duration time were similar. In the co-administration of i.v. and volatile anesthetics, the minimum heat production was significantly lower (P < 0.01) and the duration of this minimum production was significantly more sustained (P < 0.01) compared to those seen in the single administration of each anesthetic. Moreover, by measurement of the whole body heat production, the slow induction of general anesthesia markedly affected the circadian rhythm on the next postoperative day. These results indicate that the measurement of the whole body heat production will be a marker for the recovery from general anesthesia and the return to the usual life style (such as the QOL).

We have isolated new benzo[a]pyrene-resistant clones, cl-21 and cl-32, of the mouse hepatoma line, Hepa-1. CYP1A1-dependent aryl hydrocarbon hydroxylase activity is not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene in these two cell lines. However, mRNA of CYP1A1 is inducible in cl-21 and cl-32 cells, as in the wild-type cells, in spite of an undetectable level of cytosolic Ah receptor. The cl-21 cDNA of Cyp1a-1 was found to have a single mutation leading to an amino acid substitution from Leu (118) to Arg (118). However, the CYP1A1 protein band was not detected on Western immunoblots. The cDNA of cl-32 was found to have a single mutation leading to an amino acid change from Arg (359) to Trp (359). The presence of the mature protein in cl-32 was confirmed by Western blot analysis. Somatic cell hybridization experiments demonstrated that the phenotype of cl-21 and cl-32 is recessive and that these clones belong to the same complementation group. These data suggest that there may be a non-Ah receptor-mediated mechanism of CYP1A1 induction.

Changes in amino acids in liver tissue during hemorrhagic shock were examined in eight mature mongrel dogs using the microdialysis method. The mean blood pressure was maintained at 50 mmHg by exsanguination, and the values of liver tissue amino acids after 30 minutes showed significant decreases of aspartate, glutamate, histidine, glutamine, glycine and taurine. The decrease of taurine was especially marked. The values dropped further 30 minutes after returning the blood into circulation with some exceptions. These results suggest the possibility that hemorrhagic shock causes reduction in uptake of amino acids by the liver or consumption of amino acids in the liver, and that bile acid metabolism appears to be disturbed by the marked drop in the taurine level. It is necessary to give careful consideration to the possible existence of reduced amino acid metabolism in the liver in the treatment of hemorrhagic shock.

Menadione-catalyzed H2O2 production by viable cells is proportional to viable cell number. The correlations between the viable cell number and the concentration of H2O2 produced are determined with the rapid chemiluminescent assay (S. Yamashoji, T. Ikeda, and K. Yamashoji, 1989, Anal. Biochem. 181, 149-152). This chemiluminescent assay of viable cells requires only 10 min and is much faster than NR (neutral red) inclusion and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assays, which require 3-5 h. When viable cells are incubated with antitumor drugs, detergents, mycotoxins, and glycoalkaloids for 24-48 h, a decrease in menadione-catalyzed H2O2 production in a dose- or incubation time-dependent manner is observed. In general, the 50% inhibition concentration determined by the chemiluminescent assay is lower than that determined by NR inclusion and MTT reduction assays, and the order of relative cytotoxic effects of agents is the same among these assays. Furthermore, clear cytotoxic effects are observed by the chemiluminescent assay after 1 h exposure of trypsinized cells to toxic compounds. Therefore, the chemiluminescent assay is expected to be more useful for the rapid detection of cytotoxic compounds than NR inclusion and MTT reduction assays.

We measured the cardiovascular effect of, and catecholamine and other hormonal responses to, anesthetic doses of fentanyl and original NLA in 25 patients for open heart surgery. The patients were randomly divided into three groups (group N, F30, F75). During induction, in group N; droperidol 0.25 mg.kg-1 and fentanyl 5 micrograms.kg-1, in group F30; fentanyl 30 micrograms.kg-1, and in group F75; fentanyl 75 micrograms.kg-1 were administered intravenously. Additional fentanyl was administered at a rate of 100 to 200 micrograms.h-1. Droperidol 0.25 mg.kg-1 was administered in group N when cardiopulmonary bypass (CPB) was disconnected. Plasma samples were assayed for norepinephrine, epinephrine, ACTH and cortisol before and after induction, during sternotomy, 60 minutes after institution of CPB, after weaning from CPB, and before as well as after extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate pressure product (RPP) were calculated simultaneously at the blood samplings. In all groups, no remarkable change in cardiovascular dynamics was observed. CPB was associated with marked increases in catecholamines, but high dose fentanyl in dose of 75 micrograms.kg-1 was able to suppress epinephrine level more than in group N. In high dose fentanyl group (F30, F75) ACTH was within normal ranges, even during CPB. The results suggest that high dose fentanyl is a complete anesthetic in patients for cardiac surgery. But a large dose of fentanyl causes small decreases in heart rate and arterial blood pressure. Our data indicate that group F30 is an attractive anesthetic technique for patients with valvular disease.

A 54-year-old woman was treated for bronchial asthma for 14 yr. In March of 1989, chest roentgenography and computed tomography (CT) revealed development of bilateral pulmonary hilar lymph node enlargement. Positive 67Ga uptake was observed in bilateral pulmonary hili. Although levels of serum angiotensin converting enzyme (ACE) and lysozyme were within normal range, biopsy specimen of scalene lymph nodes showed noncaseating epitheloid-cell granuloma, leading to the diagnosis of sarcoidosis. Steroid therapy ameliorated both sarcoidosis and bronchial asthma. Although the association of sarcoidosis and bronchial asthma is uncommon, there may be an etiological relationship between them.

The purpose of the present study was to compare hemodialysis (HD) and push/pull HDF in terms of uremic substance removal and clinical improvement. The treatment of patients complaining of shoulder joint pain was changed from conventional HD to HD or push/pull HDF using a hemodiafilter with large membrane pores. Push/pull HDF showed significantly greater removal of beta 2-microglobulin (beta 2-m) and other small molecular proteins than HD, and serum beta 2-m was significantly lower in concentration with push/pull HDF than HD. There was a decrease in the shoulder joint pain from push/pull HDF, and the range of upper arm movement thereby increased. However, neither this decrease in pain nor the increase in upper arm movement resulted with HD treatment. Hence, it was concluded that push/pull HDF is a more effective form of therapy.

Blood and ultrafiltrate electrical resistivities were continuously monitored during hemofiltration. By substituting these values into a previously developed equation that was modified by the authors, the hematocrit value was determined; and blood volume change was obtained from the change in this value. The following facts were discovered as the result of monitoring the blood volume change during treatment: When the body position was changed from the reclining to the sitting position, the blood volume decreased by 4.2 +/- 0.3%. With the body water removal rate kept constant, the body position recumbent, and the subject fasted, the blood volume gradually decreased. However, when the position was changed from reclining to sitting for food intake and once more returned to the supine position after the meal, the blood volume was greatly affected by the change in position and the food intake.

Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.

Hemofiltration and plasma exchange, using a plasma separator with membranes, were used in 14 psoriatic patients. The efficacies of the treatments were compared. Among the patients, 13 were treated with hemofiltration and/or direct hemoperfusion, 5 experienced complete remission, 5 improved, and 3 remained unaffected. In these 3 cases, plasma exchange was performed. The first patient, who suffered from psoriasis pustulosa with arthropathica, achieved complete remission with only two treatment of 2-L plasma exchange. Joint pain was also eliminated. Both skin lesions and joint pain were markedly improved in the second patient, who suffered from psoriasis vulgaris with arthropathica. The third patient showed marked improvement with only two plasma exchanges, and is under continuing observation.

Administration of ticlopidine, a new inhibitor of platelet aggregation, during hemodialysis to two patients with thrombotic occlusion of external A-V shunts markedly suppressed the obstruction of the shunt and improved anemia. Consequently, it was concluded that this drug may be useful for maintaining good blood flow and good patency of shunts in patients undergoing dialysis. In order to determine the dialyzer efficiency during dialysis, the reduction rate of the dialyzer was determined in vitro. The dialyzer reduction rates for urea, creatinine, uric acid, and phosphoric acid were all lowered after dialysis, and the administration of ticlopidine resulted in a suppression of the drop in the reduction rate. Based on the inhibitory effect of ticlopidine on platelet aggregation, it was assumed that a close correlation may exist between adhesion and aggregation of platelets and the drop in the efficiency of the dialyzer during dialysis as well as thrombotic obstruction of shunts.

A new simultaneous hemofiltration and dialysis system was developed which has no need of infusion fluid. The system employs two hemodiafilters in a direct series. An ultrafiltration rate and dialysate flow rate control system was employed to control the dialysate flow at the inlet and outlet, and the difference in volume was arranged to be the amount of water removed from the body. When the blood circuit was narrowed between the two hemodiafilters, the ultrafiltration was performed at the first hemodiafilter; at the second one, the dialysate moved to the blood side as a dilution fluid. To remove pyrogens and bacteria, tap water was subjected to activated charcoal, ion exchange and reverse osmosis treatment, followed by preparation of the dialysate. In clinical evaluation, this system showed marked improvement in clearance of middle and large molecules.