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Background /aim Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction to drugs which characteristically occurs after a long latency period. In addition, human herpes virus 6 (HHV-6) reactivation is a characteristic finding in DIHS, which has been known to be related to disease severity. Because DIHS has generally been treated by systemic corticosteroids, the natural clinical course is not clear. Methods Data for patients with both DIHS and HHV-6 reactivation were retrospectively collected from four hospitals. Results Data were collected on 12 patients ranging in age from 21 to 76 years (median, 65.5). All cases had been suspected of DIHS at their initial visit, and the elevation of serum anti-HHV-6 antibody had been confirmed (4–256 times: median; 32). The culprit drugs were carbamazepine (6), salazosulfapyridine (4), mexiletine (1) and zonisamide (1). The period of latency from the first administration of the drug ranged from 15 to 50 days (median, 30). All patients were treated conservatively for DIHS without systemic corticosteroids. The peaks of the patients’ symptoms and laboratory findings were as follows (days from the onset of skin lesions): fever, 4–16 (median, 10.5); liver abnormality, 3–22 (median, 7.5); leukocytosis, 7–20 (median, 9). All patients recovered without pneumonia, myocarditis, nephritis or other systemic disease, from 7 to 37 days (median, 18) after withdrawal of the drug and from 11 to 44 days (median, 21) after the onset of skin lesions. Conclusion It might be unnecessary to give systemic corticosteroids immediately to all patients suspected of having DIHS.

Although power distribution lines are protected by ground wire systems, there are fears that these ground wires may break at their corrosion points. For practical purposes, they have therefore been removed to avoid maintenance in certain areas. The Tokyo Electric Power Company (TEPCO) has continuously observed lightning strokes and obtained 321 datasets to date. The present study has determined the potential for an anticipated lightning stroke attraction effect based on the observed data, despite the fact ground wires are eliminated while ground wire caps are left in place. Furthermore, a verification experiment using facilities simulating the power distribution system has confirmed the problem of insulated wires being struck by lightning and the extent of the impact of the ground wire cap on the lightning stroke attraction effect. These results are expected to provide a new facility-construction menu, which will help rationalize the lightning protection design.

Human milk (HM) contains various bioactive antioxidants. Lactoferrin (Lf) has been assumed to be one of the major antioxidants in HM. We examined the antioxidative properties of iron-unsaturated human Lf (apo-hLf, the major form of Lf in HM) in two intestinal epithelial cell lines: (1) An intestinal epithelial cell line (IEC-6) were preincubated for 24 h with either 50 microg/mL of apo-hLf, iron-saturated human Lf (holo-hLf), iron-unsaturated bovine transferrin (apo-bTf), or 800 ng/mL of the iron-chelating compound deferoxamine (DFX), followed by hydrogen peroxide (H2O2) challenge to induce oxidative stress. Survival rates were significantly higher in the cells preincubated with apo-hLf and DFX than those preincubated with holo-hLf. (2) Caco-2 cells were preincubated with or without apo-hLf for 24 h, followed by an H2O2 challenge. Intracellular oxidative stress was assessed by a fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Fluorescent intensity of cell images and cell homogenates was significantly lower in the cells preincubated with apo-hLF than those preincubated without apo-hLF. Our study indicates that apo-hLf alleviates H2O2-induced oxidative damage in intestinal cells due to the iron-chelating capacity. Therefore, Lf in HM may act as an antioxidant in the gastrointestinal tract (GIT).

Background: To evaluate the effect of n-3 polyunsaturated fatty acid (PUFA) deficiency on the development of retinal function in children with biliary atresia (BA), we examined serum fatty acid levels and performed electororetinogram (ERG) in patients with BA. Methods: The study group was composed of one male and four female BA patients (8−14 years) with serum bilirubin levels ranging from 0.40 to 1.48 mg/dL. All of the subjects were born as full-term infants. The fatty acid composition of total lipids in serum was analyzed by gas chromatography before the Kasai operation, approximately 10 months after the Kasai operation, and at the time of the ERG study. The ERG was recorded using corneal contact lens electrodes. Results: Two of the five patients showed decreased levels of arachidonic acid and docosahexaenoic acid (DHA) before and after the operation, but no abnormal findings on ERG were detected in these patients. The other three patients had decreased levels of α-linolenic acid or DHA after the operation, but again, no abnormalities were found on ERG. Conclusion: These results suggest that insufficiencies of DHA and other n-3 PUFA in full-term infants might not have an influence on later ERG results.

Very low birth weight (VLBW) infants are known to have poorly developed antioxidant system and may be at increased risk for radical damage. Previous studies have reported higher levels of lipid peroxide products in lipid emulsion used for parenteral nutrition. To examine the direct effects of parenteral lipid infusion on DNA damage in VLBW infants, we measured urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after the parenteral lipid infusion. In both the lipid-infused and lipid-free groups, urinary 8-OHdG excretion levels at 14 days old were significantly (p < 0.01) lower than those at 2 and 7 days old. However, there were no significant differences in urinary 8-OHdG excretion levels between the lipid-infused and lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral lipid infusion does not cause oxidative DNA damage, but irrespective of the infusion DNA damage during the first week of life is enhanced when compared with 14 days after birth in VLBW infants.

Both wingless worker-like queens, and dealated queens of the ponerine ant, Hypoponera nubatama, engage in egg-laying activities. Corresponding to the differentiation in female reproductives, males are also dimorphic, winged and ergatoid. In Japan, wingless reproductives appear mainly from late July to mid-August, while winged ones appear mainly from late August to mid-October. Winged reproductives make nuptial flights, while wingless ones mate inside the nests. Cross-mating is, however, possible in the laboratory. The mating of ergatoid males is characterized by very long precopulation and copulation times, frequently more than 2 hours, suggesting that ergatoid males themselves play the role of mating plug. We observed no fighting among ergatoid males. However, they did seem to cause a relatively higher mortality rate in rival ergatoid males by embracing them while still in the cocoon.

Mucosal damage is commonly observed in food-sensitive enteropathy in infants, and the generation of leukotrienes is involved in the pathogenesis of this enteropathy. Because supplementing n-3 fatty acids is known to modify the production of leukotrienes, we investigated whether a change of dietary fatty acid composition affects leukotriene synthesis and food hypersensitivity reactions in the intestine by using a mouse model of food-sensitive enteropathy. The model was prepared by feeding ovalbumin to BALB/c mice after intraperitoneal injection of cyclophosphamide. Diets were prepared from soybean oil (control), perilla oil, lard, corn oil, and 0.125 volume of corn oil (low fat diet) and given to mice for 4 wk. Villous heights, crypt depths, leukotriene B4 and C4 production in the intestine were measured. Crypt hyperplasia and villous atrophy were severer in the corn oil-fed group than those of control group, whereas mucosal damage in the perilla oil and low fat diet groups was minimal. In the corn oil-fed group, red blood cell membrane levels of n-3 fatty acids were lower than the control, and the synthesis of leukotrienes was highest among all groups. In the perilla oil and low fat diet groups, n-6 fatty acids were lower than those of control group and leukotriene production was significantly suppressed. These results indicate that reducing cell membrane levels of n-6 fatty acids by feeding less n-6 fatty acids or supplementing n-3 fatty acids, is important to suppress leukotriene biosynthesis for prevention from mucosal damage in food-sensitive enteropathy.

The objective of this study was to compare the gastric acidity patterns of patients with duodenal ulcers and normal children. Eight patients with duodenal ulcer had their intragastric pH monitored for two consecutive 24 h periods using intragastric glass electrodes. The first 24 h period elucidated pH patterns in the absence of treatment and the second period evaluated the acid suppressive effect of 15 mg/kg of cimetidine when given in three divided doses. Results showed that the ulcer patients were hyperacidic, particularly at midnight. This finding was in marked contrast to the results obtained in the study of normal controls. The mean pH of normal children was above 3 around midnight. This phenomenon is known as intragastric pH inversion. The mean pH 3 time (the cumulative duration of the time for which gastric pH is maintained at > or = pH 3) was significantly shorter in patients with ulcers. However, pH 3 time of these patients significantly increased throughout the 24 h recording period during the daytime and at night after the introduction of cimetidine. This resulted in an induction of apparent nocturnal intragastric pH inversion for the ulcer patients. This study demonstrates the usefulness of 24 h continuous intragastric pH monitoring in children. The data showed that there was a pattern of gastric hyperacidity in pediatric ulcer patients which is clearly distinct from that of normal children, particularly in the patterns occurring at midnight. Cimetidine at 15 mg/kg per day in three divided doses was effective in suppressing secretion even at night.

During the perinatal period, oxidative stress is intimately involved in pathologic processes of serious diseases. Although breast milk contains many antioxidants, it is not clear whether breast milk can act as an antioxidant in infants in vivo. We compared the oxidative stress levels in total of 41 healthy 1-mo-old infants by measuring urinary 8-hydroxy-2'-deoxyguanosine, which is one of the biomarkers of oxidative DNA damage. These infants were divided into four groups according to the type of feeding. Urinary 8-hydroxy-2'-deoxyguanosine excretion of the breast-fed group was significantly lower than those of the artificial milk dominant mixed-fed group or the bottle-fed group. Our data suggest that breast milk, not artificial formula, acts as an antioxidant during infancy.

Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction to drugs which characteristically occurs after a long latency period. In addition, human herpes virus 6 (HHV-6) reactivation is a characteristic finding in DIHS, which has been known to be related to disease severity. Because DIHS has generally been treated by systemic corticosteroids, the natural clinical course is not clear.Data for patients with both DIHS and HHV-6 reactivation were retrospectively collected from four hospitals.Data were collected on 12 patients ranging in age from 21 to 76 years (median, 65.5). All cases had been suspected of DIHS at their initial visit, and the elevation of serum anti-HHV-6 antibody had been confirmed (4-256 times: median; 32). The culprit drugs were carbamazepine (6), salazosulfapyridine (4), mexiletine (1) and zonisamide (1). The period of latency from the first administration of the drug ranged from 15 to 50 days (median, 30). All patients were treated conservatively for DIHS without systemic corticosteroids. The peaks of the patients' symptoms and laboratory findings were as follows (days from the onset of skin lesions): fever, 4-16 (median, 10.5); liver abnormality, 3-22 (median, 7.5); leukocytosis, 7-20 (median, 9). All patients recovered without pneumonia, myocarditis, nephritis or other systemic disease, from 7 to 37 days (median, 18) after withdrawal of the drug and from 11 to 44 days (median, 21) after the onset of skin lesions.It might be unnecessary to give systemic corticosteroids immediately to all patients suspected of having DIHS.

The incidence of Helicobacter pylori infection and effects of H. pylori colonization on mucin content and mucosal inflammation of the antral mucosa were studied quantitatively in 55 Japanese children with suspected gastritis and peptic ulcers (aged 6-16 years, mean 12.3 years). H. pylori was detected, using Warthin-Starry stain, in nine of the 22 cases (41%) with antral histological gastritis, but in none of the 33 histologically normal cases. Five out of seven duodenal ulcer cases showed histological gastritis, and all five cases were H. pylori positive. Severity of gastritis, evaluated by means of gastritis score, was significantly higher in H. pylori positive gastritis cases than in H. pylori negative gastritis cases (5.4 +/- 1.0 vs 3.1 +/- 0.3, P < 0.001). A PAS-AB index, a proportion of the periodic acid Schiff-alcian blue (PAS-AB) positive mucin area to the total epithelial area, was significantly lower in H. pylori positive cases than in H. pylori negative cases, irrespective of the existence of histological gastritis (23.5 +/- 7.6% vs 40.4 +/- 5.5%, 43.5 +/- 4.2%, P < 0.001). The decreased mucin content of gastric mucosa is likely to lead to weakening of an important defensive factor of gastric mucosa. These findings suggest that H. pylori plays an important role in gastritis and peptic ulcers in children, especially in cases with duodenal ulcer.

It has been well established that β-amyloid peptide is the principal protein component of extracellular cerebral amyloid deposits in patients with Alzheimer's disease (1,2). β-Amyloid is derived from a large precursor protein, amyloid precursor protein (APP), which is an integral membrane protein, with a receptor-like structure (3). APP is a member of a gene family which encodes extremely well-conserved membrane proteins. APP/APP-like genes have been isolated from various species including fly (4), nematode (5), and fish (6). In mammals, two APP-like genes, amyloid precursor-like protein 1 (APLP1) and 2 (APLP2), have been isolated (7,8). The amino acid sequences of these APP family proteins are highly conserved, especially in the cytoplasmic domain, except that unlike APP, APP-like proteins lack the β-amyloid sequence. It has been thought that APP and APLP2 have a similar physiological function (9). In contrast, APLP1 is believed to differ functionally from APP and APLP2, although the physiological functions of these APP family proteins have not yet been well analyzed.

In an attempt to investigate the causes of common bile duct dilatation (CBDD), activity of the pancreatic enzymes in bile aspirated from the dilated duct during laparotomy was measured in 24 children with CBDD. The reasoning behind this is the fact that the existence of activated pancreatic enzymes, namely raised activity of all enzymes accompanied by trypsin activation, can be regarded as an acquired result of an anomalous choledochopancreaticoductal junction (ACP-DJ). All of the pancreatic enzymes measured were activated in 14 cases (58.3%) but no evidence of activation of enzymes, such as trypsin or others except for amylase and lipase, was observed in the remaining 10 cases (41.7%), whether an ACPDJ was present or absent. Eight of the 10 patients with no enzyme activation (33.3% of the total) were less than 2 months old. The findings in these eight infants, which included cystic dilation or hypoplasia of the intrahepatic duct, provide strong suggestive evidence of the congenital nature of these cases. These results suggest that at least one third of CBDD cases are congenital and the remaining cases are either acquired or a combination of congenital and acquired, or both.

A compact atomic force microscope that can easily find and position the surface point to be measured has been developed. Tip spring displacement is detected using an optical sensor that detects the focusing error. The objective lens of this sensor is also used to project an optical image of the sample surface onto a CCD image sensor. A micro-step XY stage mechanism has been developed to move a sample over a wide range. When a single cosine waveform voltage is applied to a piezoelectric tube scanner, the quick bending motion causes the sample holder to progress by frictional force. This mechanism can drive the sample holder two-dimensionally in μm-order steps. Using this mechanism, the point to be measured is easily positioned. Subsequently, the sample is moved by the same tube scanner with the usual scanning mode of an atomic force microscope. This atomic force microscope is compact and stable, because no additional XY stage is necessary to position a sample.

Very thin films of perfluoroalkylpolyether (Rf) derivatives having benzene rings on carbon surfaces were evaluated using scanning tunnelling (STM) and frictional force (FFM) microscopes. Two kinds of surface were used as substrates: one was highly oriented, pyrolytic graphite (HOPG) as a defect-free and inactive surface, and the other was sputtered carbon as an active surface having many defects. STM was used to observe the configuration and mobility of lubricant molecules and clusters on the HOPG. The STM images reveal that the lubricant molecules in clusters are not fixed but can easily change positions. FFM was used to evaluate frictional force characteristics on the non-lubricated and lubricated sputtered carbon films. On sputtered carbon film even the lubricants that had insufficient stability on HOPG proved to be stable and able to decrease the friction. The adsorption mechanism of a lubricant on a practical sliding surface that is active and has many defects, such as sputtered carbon, is different from that on a defect-free and inactive surface such as HOPG.

Experimental results are reported on heat transfer in small disk enclosures (DEs) containing several 5.25-inch-diameter disks and two symmetrical brushless DC motors mounted on a spindle. Windage loss decreases with disk diameter, and the ratio of windage loss in the 5.25-inch-diameter disk to that in 10.5-inch-diameter disks is 1/16. Air flow over the disk surface is probably turbulent at rotation speeds of more than 5400 RPM. The windage loss dominates the total at rotation loss speeds of more than 5400 RPM. An effective forced convection suppresses the temperature increase of the DE to less than 5 degrees C, due to the higher thermal conductivity of the DE surface. High track densities of more than 100 tracks/mm are feasible as a result of the low thermal off-tracking, less than 0.3 mu m, and the small deviation in head positioning, less than 0.5 mu m. These low values arise from the thermally and mechanically symmetrical DE structure and a ceramic positioner with high stiffness. >

We report a case of Dubin-Johnson syndrome (DJS) with severe infantile cholestasis and elevated computed tomography (CT) attenuation of the liver. Increased levels of urinary coproporphyrin I were found as well as pigment granules in the hepatocytes and hepatosteatosis. The CT attenuation was markedly higher in the liver of this patient at the ages of 3 and 7 months than in the spleen or kidneys. This high attenuation may be a finding specific to infantile DJS and, therefore, abdominal CT may be helpful in the diagnosis.

Objective: Oxidative stress is intimately involved in the pathologic processes of serious diseases in the perinatal period. Human milk (HM) contains various bioactive substances, some of which are known as antioxidants, including polyamines such as spermine (SPM). We examined the antioxidative properties of HM and SPM in an intestinal epithelial cell line. Method: Confluent Intestinal Epithelial Cells-6 (IEC-6) cells were preincubated with 100-fold dilutions of defatted HM, bovine milk, or three artificial milks for 24 hours, followed by hydrogen peroxide (H 2 O 2 ) challenge (0.5 mM, 30 min) for oxidative stress. Cells were preincubated with either HM or increasing concentrations (within the range of HM) of SPM for 24 hours followed by an H 2 O 2 challenge (0.25 mM, 30 min). Results: HM-treated cells showed the highest survival rate (50%) compared with no pretreatment (27%), bovine milk-treated (6%), or artificial formula-treated (13-16%) cells. Significantly higher survival rates were observed in the cells treated with HM (44.0%) and in those treated with 0.5, 1, or 5 μM of SPM (12.6, 13.1, or 22.2%, respectively) in comparison with the nontreated cells (7.0%). Conclusion: Our results demonstrated that HM and SPM alleviated H 2 O 2 -induced oxidative damage in IEC-6 cells, whereas bovine milk and artificial formula did not show any antioxidative capacity. These results suggest that HM acts as an antioxidant in the gastrointestinal tract of infants and that SPM plays an important role in the antioxidative properties of HM.

Background: Human milk contains many kinds of antioxidant and is considered to prevent diseases mediated by oxygen free radicals in very low birthweight (VLBW) infants. Aims: To examine the antioxidant effects of breast milk in VLBW infants by determining urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, which is known to be a non-invasive marker for in vivo oxidative DNA damage. Methods: Urinary 8-OHdG concentrations were measured in 15 breast fed and 14 formula fed VLBW infants at 2, 7, 14, and 28 days of age. Results: Urinary 8-OHdG excretion at 14 and 28 days of age was significantly lower than at 2 and 7 days of age in the breast fed group, and significantly lower than in the formula fed group. Conclusion: This is the first direct evidence of the antioxidant action of human milk in VLBW infants.

A new pre-assembled (PRE-ASSE) ferrule has been developed for use in SC connectors that simplifies and automates SC connector assembly. The PRE-ASSE ferrule consists of a zirconia ferrule, a rear outer shell, a coil spring, and a newly developed plate spring. The features are as follows: 1) The tolerance of the loss increment caused by fiber-cable pulling and bending is almost the same as that of a conventional SC connector. 2) It is possible to orient the fiber-core eccentricity. 3) The SC connector can be easily assembled manually. These features are achieved by the loosely coupling mechanism using the newly developed plate spring. The characteristics of this SC-type optical fiber connector are almost the same as those of a conventional one. >

Experimental results of heat transfer in helium-gas-enclosed disk enclosure (DE) are described. The following results were obtained. (1) The windage loss of a DE containing helium gas is about one fifth of that of a DE containing air. This effectively decreases DE temperature and disk runout. (2) The temperature increase of the positioner coil in helium gas is about one half of that in air. (3) Smaller windage loss and high conductivity minimize helium gas locational temperature dependence. >

Maintaining high cell viability during cell culturing is an effective way to improve the production yield in mammalian cell culture. In this study, we examined the effect of temperature shifts under pH control conditions on cell growth and human antibody production in Chinese hamster ovary (CHO) cells using a 3-L bioreactor. Shifting the temperature and timing significantly influenced the cell proliferation rate and antibody productivity. When we shifted the culture temperature from 37°C, to 31°C before the stationary growth phase at pH 6.8, cell viability remained high and the final antibody concentration increased up to 2-fold compared to the culture at 37°C in the same culture period. However, there were no significant effects on the cell viability or the productivity with a temperature shift to 31°C at pH 7.0 or with a temperature of 37°C at pH 6.8. We also confirmed these results in larger-scale bioreactors (100 L and 1000 L), which suggested that the elevated pCO2 level observed in the larger reactor did not influence both cell growth and antibody production in the downshift temperature condition.

In our previous study, we developed a novel cycloheximide resistance (cyh R) marker for use in mammalian cells. In experiments using human monoclonal antibody genes, vectors containing this cyh R marker produced cycloheximide resistant CHO clones whose maximum expression levels were significantly higher than that of the neo R/G418 clones. The expression levels of cyh R clones were 3 to 4 times higher than those of neo R clones, in protein-free suspension culture. The maximum yield of antibody in cyh R clones reached over 700 mg/L in a typical fed-batch culture using a 3L-bioreactor. Cell growth studies showed no difference in doubling times between cyh R and neo R clones expressing antibodies and stability of expression in the absence of antibiotic was also demonstrated. The cyh R system thus provides a significantly more efficient method for selection of high-expressing CHO clones without the need for gene amplification, and in a substantially shorter time frame than methods currently in use.

A 0.5 /spl mu/m CMOS gate array family with high speed modules is discussed. Measured access time of the 8 Kbit 2-port metallized RAM is 6.3 ns. Simulated access time of the 16 Kbit diffused RAM is 5.5 ns. Propagation delay time of the 2-input NAND is 200 ps at a standard load. Use of high performance internal logic circuits, high speed compiled RAM, improved GTL (Gunning Transceiver Logic), and PLL (Phase Locked Loop) realizes operation of over 100 MHz at 3.3 V. This 3F (Flexible, Fast, and Friendly) ASIC family can be applied to high speed processors in workstations and graphics equipment. >

Estrogen plays an important role in many physiological events including carcinogenesis and the development of human breast cancer. However, the molecular mechanisms of estrogen signaling in cancers have not been clarified hitherto and accurate therapeutic prediction of breast cancer is earnestly desired. We first carried out estrogen-responsive expression profiling of approximately 9000 genes in estrogen receptor-positive human MCF-7 breast cancer cells. Based on the results, estrogen-responsive genes were selected for production of a custom-made cDNA microarray. Using a microarray consisting of the narrowed-down gene subset, we first analyzed the time course of the estrogen-responsive gene expression profiles in MCF-7 cells, resulting in subdivision of the genes up-regulated by estrogen into early-responsive and late-responsive genes. The expression patterns of several genes were confirmed by Northern blot analysis. We also analyzed the effects of the estrogen antagonists ICI 182780 and 4-hydroxytamoxifen (OHT) on the estrogen-responsive gene expression profiles in MCF-7 cells. While the regulation of most of the genes by estrogen was completely abolished by ICI 182780, some genes were partially regulated by estrogen even in the presence of OHT. Furthermore, the estrogen-responsive gene expression profiles of twelve cancer cell lines derived from the breast, ovary, stomach and other tissues were obtained and analyzed by hierarchical clustering including the profiles in MCF-7 cells. Several genes also showed up-regulation or down-regulation by estrogen in cell lines other than MCF-7 cells. The significance of the estrogen-responsive genes identified in these analyses concerning the nature of cancer is discussed.

Aims: We investigated the effect of n–3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). Methods: We fed Wistar rats a perilla oil-enriched diet containing α-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing α-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. Results: The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB4 and LTC4 from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. Conclusion: These results suggest that n–3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis.

Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 +/- 0.81, 1.65 +/- 0.63, and 0.93 +/- 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P0.0001). This association was evident for each group studied (P0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels.

Recent advances of lipoprotein metabolism abnormality were reviewed. Recombinant apolipoprotein and transgenic mice expressing high levels of apolipoproteins or apolipoprotein deficient mice produced by gene targetting technique are providing important information on effect of lipoprotein metabolism. We made novel mouse cuff injury model for transgenic mice and knock-out mice. This injury model will also provide important information on intimal thickening using transgenic mice and knock-out mouse.

Background: It is believed that the incidence of cystic fibrosis (CF) among Asiatic races, including the Japanese, is very rare. This epidemiological study was carried out to investigate the incidence of CF in Japan. Methods: We collected literature describing CF cases among pure Japanese and found 124 cases reported as CF during the 43 years from 1951, when the first case was reported, to 1993. Only 104 cases (57 male and 47 female patients) of 124 cases met our diagnostic criteria. Results: A simple calculation based on the number of reported CF cases and of live births after 1980 suggested that the incidence of CF is about 1 in 350,000 in the Japanese population. Twenty-nine (27.9% of the total) of 30 patients diagnosed in the neonatal period presented symptoms of meconium ileus, an incidence higher than that reported for the white population. Conclusions: Our study results suggest that the incidence of CF in the Japanese population is even rarer than had been estimated before and that there is a genetic difference between northern European and Japanese populations.

In an attempt to elucidate the etiology of Kawasaki disease (KD), the microflora of the small intestine was investigated in 15 Japanese KD patients. The range of bacterial species adhering to the lumen of the jejunum of KD patients was quite different from that of controls. A wider variety of bacteria was isolated from jejunal biopsies in the acute phase of KD as compared with those from control children. Gram-positive cocci were isolated from KD patients predominantly. Notably, five kinds of streptococci and two kinds of staphylococci were isolated only from KD patients. Further investigation of the microflora of the small intestine of KD patients may provide clues to clarify the pathogenesis of this disease.

The current study tested the hypothesis that the gastrointestinal tract could be one of the primary sites of entry for etiologic agents in Kawasaki disease (KD). In an attempt to elucidate the pathogenic role of certain superantigenic agents in KD, T cell receptor V beta expression by T cells in the small intestinal mucosa of KD patients was investigated using MAb on frozen tissue sections. Twelve Japanese patients with KD and eight controls were enrolled in the study. The numbers of cells stained by an immunofluorescence from each study group were counted and analyzed statistically by the t test. The occurrence of V beta 2+ T cells was found to be selectively increased in the small intestinal mucosa of patients in the acute phase of KD compared with controls (p0.01). In our previous study, five kinds of streptococci and two kinds of staphylococci, not detected in control patients, were isolated from the lumen of the jejunum of KD patients. These data suggest that the increased occurrence of V beta 2+ T cells in the jejunal mucosa of KD patients may be caused by exotoxins acting as superantigens produced by bacteria colonizing the small intestinal mucosa of these patients.

We collected 104 CF cases among pure Japanese patients from the literature covering a period of 42 years from 1951 to 1993. A simple calculation based on the numbers of reported cases and live births in the period suggests that the estimated incidence of CF might be about one in 680 000 in the Japanese population. Twenty-eight percent of the total cases presented symptoms of meconium ileus, which is a higher frequency than that seen in the Caucasian population. This might probably reflect a genetic difference between CF of Northern Europe and Japan.

The efficiency of the 13C-Urea Breath Test (13C-UBT) for the detection of Helicobacter pylori colonization in gastric mucosa was evaluated. The 13C-UBT was performed in five pediatric and six adult subjects who had had upper gastrointestinal endoscopy within 2 weeks. H. pylori colonization was confirmed in two pediatric and three adult subjects with peptic ulcer combined with antral gastritis, by histological examination of antral biopsy specimens. When an individual with H. pylori colonization ingested a solution containing 13C-urea, a significant amount of 13CO2 appeared in the respiratory CO2 within 10 min. The mean cumulative percentage dose of 13C recovered in the breath over 30 min in the cases with H. pylori colonization was significantly higher than that in those who were not colonized (4.91 vs 0.41, P < 0.001). In addition, the effect of antibiotic on the eradication of H. pylori from gastric mucosa was monitored by 13C-UBT in two cases. The values of cumulative percentage dose of 13C over 30 min fell to the same levels as those observed in H. pylori negative subjects after just 2 weeks treatment with amoxicillin; however, positive results were obtained again 1 month after the withdrawal of amoxicillin. In summary, 13C-UBT is a simple, reliable, non-invasive method in the diagnosis of gastric H. pylori colonization especially for pediatric patients.

Summary Quantitative analysis and immunohistochemical studies of small intestinal mucosa were performed to investigate the mechanism of mucosal damage in 10 patients with food-sensitive enteropathy. Jejunal biopsy specimens were taken before and after treatment and after clinical relapse following a challenge test. The low villous height of untreated patients normalized after introduction of an elimination diet but declined again to subnormal level after a challenge test. Several other types of cells were significantly increased in the untreated patients in comparison to controls. These included HLA-DR+ (DR + ) CD4+ cells in the lamina propria and intraepithelial CD8+ cells. Moreover, those cell patterns, such as increased DR+ CD4+ cells and CD8+ cells, normalized with treatment but regressed to pretreatment levels when the patients were challenged. These findings suggest that activated CD4+ cells in the lamina propria of the small intestinal mucosa, probably by releasing cytokines, may play an important role in contributing to mucosal damage in patients with food-sensitive enteropathy.

Previous reports have shown that gastrointestinal epithelial cells produce insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions of IGF. This study aims to examine the relationship between differentiation and IGF-BP secretion by human intestinal epithelial cells and the effect of growth factors on their production. Caco-2 cells were cultured in serum-free media. IGF-BP secretion into the incubation media was analyzed by Western ligand blotting and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4. Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4 secretion diminished. The effect of exogenous growth factors on IGF-BP secretion was maximal at earlier stages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4 production but stimulated IGF-BP-2 and IGF-BP-3. In conclusion, the profile of IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP production during differentiation.

To evaluate the role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer in children, ultrastructural changes of the gastric mucosa with H. pylori colonization were studied in two pediatric patients with duodenal ulcers. The study demonstrated that H. pylori: (i) colonized the mucous layer covering normal gastric epithelium; (ii) lay atop short, irregular microvilli and at the intercellular junctions of damaged cells; and (iii) adhered firmly by specific junction zone (firm connection) and loosely by filamentous appendages to the epithelial surfaces of cells which lacked evidence of a protective mucous layer. The ultrastructural changes, which become progressively worse from patterns (i) to (iii) mentioned above, suggest that these patterns represent distinct and successive stages of the infection. These findings, therefore, lend support to the notion that H. pylori infection is quite common and may relate to the pathogenesis of gastritis and peptic ulcer in children as well as in adults.

The clinical value of QRST isointegral maps (I-maps) for the detection of myocardial infarction (MI) in the presence of left bundle branch block (LBBB) was investigated. We recorded I-maps during sinus rhythm and right ventricular (RV) pacing, which simulated LBBB, in 62 patients with MI (42 patients had at least one akinetic segment and the remaining 20 patients had only hypokinesis or normal contraction) and 26 patients without MI. An abnormal decrease in the QRST value of the I-map was assessed by the difference map (D-map), which indicated a ‘−2SD area’, where the QRST integral value was less than the lower limit of the normal range (mean −2SD) calculated from 608 normal individuals. The I-maps recorded during the two activation sequences were similar to each other in patients with and without MI (r = 0.87 and 0.92, respectively). The ‘−2SD area’ was located over the left anterior chest in patients with an anterior MI and over the lower torso in patients with an inferior MI during each activation sequence. We were able to diagnose MI during simulated LBBB with a sensitivity of 84%, a specificity of 81% and a diagnostic accuracy of 83% when we used the criterion that MI is present if the sum of QRST integral values below the normal range (ΣDM) exceeds 100 mV.ms. We were able to diagnose an akinesis with a sensitivity of 81%, a specficity of 85% and a diagnostic accuracy of 83% when we used the criterion that akinesis is present ΣDM exceeds 500 mV .ms during simulated LBBB. These findings demonstrate that I-maps may be useful in detecting the presence of MI and estimating severity of asynergy in patients with LBBB.

To assess the effects of right ventricular (RV) pacing on body surface QRST distributions, we recorded QRST isointegral maps (I-maps) during sinus rhythm and RV pacing in 25 patients with anterior myocardial infarction (MI), 19 with inferior MI, and 14 without MI. The QRST values at each lead point recorded during sinus rhythm and RV pacing with an 87-lead system were analyzed with a paired t-test in each patient. An abnormal decrease in the QRST value of the I-map was assessed by the difference map, which indicated a "-2SD area," where the QRST integral value was less than the normal range (mean - 2SD) calculated from 608 normal individuals. The I-maps were similar during the two activation sequences in patients with and without MI. However, during RV pacing, QRST values significantly decreased over the upper right anterior chest and increased over the lower left anterior chest and back. The sigma DMs (sum of QRST integral values below the normal range) for both activation sequences were strongly correlated in patients with anterior MI and with inferior MI (r = 0.91 and r = 0.92, respectively; P0.001). Although small but significant changes in QRST values were detected, the distribution of the "-2SD area" and the sigma DM were similar during both activation sequences in patients with prior MI. Thus, these findings demonstrate that an altered activation sequence produces small but significant changes in QRST values but that I-maps still provide information that is useful for the diagnosis of MI during RV pacing.