Inhibition of LDL oxidation by cocoa.
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Adult↗
Biomedical subjects
H Itakura
Publications and source records attributed to H Itakura.
Regulation of fatty acid synthase expression by cholesterol in human cultured cells.
The regulation of fatty acid synthase (FAS) expression by sterols in a cultured human hepatoblastoma cell line, Hep G2, was studied. When cells were treated with compactin in a medium containing lipoprotein deficient serum, FAS mRNA level increased 1.6-fold. A squalene synthase inhibitor, TAN1607A, decreased both free and esterified cholesterol contents in Hep G2 cells and increased mRNA levels for FAS, HMG-CoA reductase, squalene synthase and LDL receptor. However, for the increment of FAS mRNA, a 10-fold higher concentration of this inhibitor was needed. These results demonstrate that the concentration of cellular cholesterol which regulates FAS expression is necessarily lower than the levels which regulate other sterol sensitive genes. FAS mRNA was also increased by an inhibitor of SREBP degradation as well as chenodeoxycholic acid. These results indicate that FAS mRNA expression is regulated by cholesterol and is mediated through SREBPs. The implications of the different modes of sterol regulation of FAS and LDL receptor expression are discussed.
Bridged Bicyclo Compounds, Heterocyclic↗
Presence of granulosa cells during oocyte maturation improved in vitro development of IVM-IVF bovine oocytes that were collected by ultrasound-guided transvaginal aspiration.
The effects of granulosa cells in maturation media on male pronuclear formation and in vitro development of in vitro-matured and fertilized (IVM-IVF) bovine oocytes were examined. In Experiment 1, cumulus-oocyte complexes (COCs) were aspirated from follicles of slaughterhouse ovaries and classified into 4 morphological categories according to the surrounding cumulus cells: Grade 1 (> 4 layers), Grade 2 (3 to 4 layers), Grade 3 (1 to 2 layers) and Grade 4 (denuded). Oocytes were co-cultured with or without granulosa cells (1 x 10(6) cells/ml) for 21 to 22 h. At 18 and 192 h after insemination, the abilities of oocytes to form a male pronucleus and develop up to the blastocyst stage in vitro were determined, respectively. The presence of granulosa cells during maturation did not affect (P < 0.05) the ability of oocytes in Grades 1 and 2 to form a male pronucleus and to develop to the blastocyst stage in Grades 1 and 4. However, the incidence of male pronuclear formation in Grades 3 and 4 and in vitro development to the blastocyst stage in Grades 2 and 3 was higher (P < 0.05) when COCs were cultured in the presence of granulosa cells than when cultured in the absence of granulosa cells. In Experiment 2, COCs collected by ultrasound-guided aspiration were co-cultured with or without granulosa cells, fertilized and cultured as described above. The incidence of blastocysts at 192 h after insemination was higher (P < 0.05) when COCs were cultured for maturation in the presence of granulosa cells (24%) than in the absence of granulosa cells (12%). These results demonstrate that supplementation of maturation medium with granulosa cells improves the quality of oocytes with relatively few cumulus cell layers, as determined by male pronuclear formation and in vitro development. We also conclude that this supplementation effectively improves the developmental ability of bovine IVM-IVF oocytes that were collected by ultrasound-guided transvaginal aspiration.
Journal Article↗
High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils.
Mice fed a high-fat diet develop hyperglycemia and obesity. Using non-insulin-dependent diabetes mellitus (NIDDM) model mice, we investigated the effects of seven different dietary oils on glucose metabolism: palm oil, which contains mainly 45% palmitic acid (16:0) and 40% oleic acid (18:1); lard oil, 24% palmitic and 44% oleic acid; rapeseed oil, 59% oleic and 20% linoleic acid (18:2); soybean oil, 24% oleic and 54% linoleic acid; safflower oil, 76% linoleic acid; perilla oil, 58% alpha-linolenic acid; and tuna fish oil, 7% eicosapentaenoic acid and 23% docosahexaenoic acid. C57BL/6J mice received each as a high-fat diet (60% of total calories) for 19 weeks (n = 6 to 11 per group). After 19 weeks of feeding, body weight induced by the diets was in the following order: soybean > palm > or = lard > or = rapeseed > or = safflower > or = perilla > fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (approximately 21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard (approximately 17.6 mmol/L), mild for perilla, fish, and palm oil (approximately 13.8 mmol/L), and minimal for high-carbohydrate meals (approximately 10.4 mmol/L). Only palm oil-fed mice showed fasting hyperinsulinemia (P < .001). By stepwise multiple regression analysis, body weight (or white adipose tissue [WAT] weight) and intake of linoleic acid (or n-3/n-6 ratio) were chosen as independent variables to affect glucose tolerance. By univariate analysis, the linoleic acid intake had a positive correlation with blood glucose level (r = .83, P = .02) but not with obesity (r = .46, P = .30). These data indicate that (1) fasting blood insulin levels vary among fat subtypes, and a higher fasting blood insulin level in palm oil-fed mice may explain their better glycemic control irrespective of their marked obesity; (2) a favorable glucose response induced by fish oil feeding may be mediated by a decrease of body weight; and (3) obesity and a higher intake of linoleic acid are independent risk factors for dysregulation of glucose tolerance.
Animals↗
Regenerative pattern of liver cells in primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related) and hepatocellular carcinoma: comparative analysis by computerized morphometry.
Computerized morphometrical measurements were made of liver cells and their nuclei taken from biopsy specimens of primary biliary cirrhosis (PBC), alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related), and hepatocellular carcinoma (HCC). The specimens were stained with hematoxylin-eosin (HE), Mallory's stain for collagen fibers, orcein method, periodic acid Schiff (PAS) reaction, and silver impregnation. Light microscopic views were then selected and original liver cells were magnified x 1000. The size of liver cell nuclei, distance between corresponding liver cell nuclei and distribution pattern of hepatocytes were calculated by computer. Variation in regenerative activity among the four disease groups was noted. Regenerative features of liver cells were mild in degree in PBC. In alcoholic cirrhosis, regenerative features of liver cells were less prominent than in posthepatitic cirrhosis. In posthepatitic cirrhosis, regenerative liver cells were well developed, showing remarkable pleomorphism of liver cell nuclei and expansive arrangement of liver cell cords. This tendency towards regenerative activity suggests that the possibility of HCC occurring is greater in posthepatitic cirrhosis than in PBC or alcoholic cirrhosis. It was concluded that morphologically, there is a greater possibility of occurrence of HCC in posthepatitic cirrhosis than in any other type of cirrhosis, because of its high regenerative hepatocytic activity. Also etiological factors of liver diseases are more important in the development of liver cell regeneration. Furthermore, regenerative activity can be measured by computerized morphometry as an established methodology.
Adult↗
Analysis of (-)-epigallocatechin gallate in human serum obtained after ingesting green tea.
A method for analyzing the EGCg concentration in human serum was developed by using high-performance liquid chromatography with electrochemical detection. EGCg was detected in human serum after the ingestion of 5 g of green tea powder (matsu-cha) dissolved in 200 ml of hot water. The concentration of EGCg in the serum reached the highest level about 2 h after ingesting the green tea, and then decreased.
Antimutagenic Agents↗
Production and transfer of IVF embryos from individual inhibin-immunized cows by ultrasound-guided transvaginal follicular aspiration.
Ultrasound-guided transvaginal follicular aspiration (UTA) was performed on 8 multiparous Japanese Black cows which had not been successful in a conventional superovulation program. These cows were actively immunized with a synthetic peptide replica of porcine inhibition alpha N1-26 (pINH) conjugated with rabbit serum albumin (RSA) using Freund's complete adjuvant. Booster injections of the peptide were given at 6, 10, 14 and 20 wk after the primary injection. Twelve follicular aspirations were performed between 10 and 33 wk after the primary injection. Cumulus-oocyte complexes (COCs) were aspirated from follicles > or = 2 mm in diameter. The recovered COCs were classified into 5 categories according to the surrounding cumulus cells: Grade 1 (> 4 layers), Grade 2 (3 to 4 layers), Grade 3 (1 to 2 layers), Grade 4 (denuded) and Grade 5 (expanded and fluffy cumulus cell mass or degenerated ooplasm). The recovered COCs available for in vitro fertilization (IVF; Grades 1, 2, 3 and 4) were matured with granulosa cells (1 x 10(6) cells/ml) for 20 to 23 hr, fertilized with frozen-thawed spermatozoa, and cultured in vitro. At day 7 after insemination, a portion of the embryos were transferred to Holstein heifers. There were great variations among donors in the number of recovered COCs in the numbers of COCs in each grade, and also in the developmental ability of fertilized COCs. IVF procedures were carried out on 685 oocytes and produced 120 embryos (17.5%). The transfer of 36 fresh IVF embryos resulted in 20 pregnancies (55.6%) at 60 days after the transfer. This study has demonstrated first, that the number of COCs collected from individual inhibin-immunized cows by UTA greatly varies among donors. Second, recovered COCs vary greatly in the classification of the morphological categories of surrounding cumulus cell mass among donors and had different developmental abilities when they were cultured after fertilization in vitro. Third, the production of pregnancy in previously nonproductive problem donors is possible using the UTA technique.
Animals↗
Dose-dependent effect of niceritrol on plasma lipoprotein-a.
Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.
Aged↗
The pattern of pediatric solid malignant tumors in western Kenya, east Africa, 1979-1994: an analysis based on histopathologic study.
This study analyzed histopathologic specimens of 600 pediatric solid malignant tumors seen during the period 1979-1994 at the histopathology laboratories of the Rift Valley Provincial General Hospital in Nakuru, the Nyanza Provincial General Hospital in Kisumu, and the Uasin Gishu Hospital in Eldoret in western Kenya. The crude incidence rate of each malignancy per 100,000 children per year was calculated. The patterns of malignancies were examined with a focus on tumor incidence, age, sex, geographic, and ethnic distribution to relate the tumors to putative environmental and genetic causative factors. The six common tumors were Burkitt's lymphoma (33.5%), non-Hodgkin's lymphoma (21.8%), retinoblastoma (11.5%), Kaposi's sarcoma (6.1%), nephroblastoma (4.5%), and Hodgkin's disease (4.1%). Significantly high crude incidence rates for lymphomas and Kaposi's sarcoma showed a characteristic ethnogeographic distribution. The majority of the tumors were found concentrated around Lake Victoria and showed decreasing occurrence as one moved towards the semi-arid and highland areas. We concluded that environmental factors seem to play a major role in childhood tumors in western Kenya.
Adolescent↗
Short report: herpes-like DNA sequences in African-endemic and acquired immunodeficiency syndrome-associated Kaposi's sarcoma.
Recently, the unique nucleic acid closely related to the herpes-like sequences has been found in acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). We have confirmed the presence of herpes-like DNA sequences in six cases of AIDS-associated KS and three of the nine cases of African-endemic KS in adults, but not in eight cases of KS in children from the same area. These sequences were seen in a histologically early stage of KS. Our results suggest that herpes-like DNA sequences may play an important role in the pathogenesis of AIDS-associated KS.
Acquired Immunodeficiency Syndrome↗
[Clinical evaluation of grade 3 superficial bladder cancer].
PURPOSE: To evaluate the treatment of grade 3 superficial bladder tumor, retrospective analysis of superficial bladder tumors was performed with special references to tumor progression and prognostic factors. MATERIALS AND METHODS: From 1976 to 1994, 247 cases with pTa-pT1 superficial bladder tumor were treated. Mean duration of follow up 77.3 months. These patients were divided into pTa (196), pT1 (52), grade 1 (61), grade 2 (196) and grade 3 (62). The prognostic factors were calculated with multivariate and univariate analysis. Tumor progression was defined as muscle invasion or distant metastasis. RESULTS: G3 tumor showed poor prognosis and was more frequent in tumor progression compared with G1 and G2 tumors (19.4% vs 0% and 1.6%). According to multivariate analysis, significant variables for actual survival rate were patient age and tumor grade. Tumor grade, recurrence and tumor configuration were also significant risk factor for cause-specific survival rate. By univariate analysis, patient age, tumor configuration, tumor size, multiplicity and concomitant CIS in G3 group were different from the other two G groups. In the G3 group, only recurrence was the predictable factor for progression. Analysis of prognosis and therapeutic modality revealed that G1 and G2 tumors were sufficiently controlled by endoscopic treatment. On the other hand, 21 cases (33.9%) of G3 tumor required total cystectomy after all. 11 cases of G3 group died of bladder cancer. Lymphatic involvement was detected in some cases of G3 tumor even if superficial. This factor showed a little relevance to poor prognosis of G3 tumor. CONCLUSION: Tumor grade was thought to be the most important risk factor of superficial bladder tumor. These results suggested that total cystectomy should be considered for the treatment of superficial G3 bladder cancer when recurrence occurs or conservative treatment is though to be failed.
Aged↗
Morphometry in histopathology. An image analysis workstation for the pathology laboratory.
OBJECTIVE: To investigate the value of morphometry in comparative histologic analysis of diseases, fixing a set of parameters suitable for analysis and to create a general strategy for data storage and economical data management. STUDY DESIGN: To establish the following fundamental principles for morphometric measurements: (1) linear measurements to determine the distance between two points by using an eyepiece graticule with an engraved scale or alternatively with a ruler on a projected microscopic image or photograph; (2) Stereology based on geometric probability, allowing features in three dimensions to be measured from two-dimensional images; and (3) a computerized image processing and analysis system for image capture, storage and analysis using specialized software and hardware. RESULTS: Measurement procedures were demonstrated in different parameters using regenerative nodules of alcoholic cirrhosis as a model. Comparative analysis between primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis and hepatocellular carcinoma showed the highest regenerative activity in posthepatitic cirrhosis. CONCLUSION: With current advances in computer technology, rapid, automatic measurements can be made from tissue sections and a variety of practical applications for the pathology laboratory, such as nuclear morphometry for comparison of different kinds of liver diseases, including classification of hepatocellular carcinoma.
Humans↗
Clinico-pathological predictive factors of response to interferon therapy in chronic hepatitis C.
We performed a clinico-pathological study to determine which pre-treatment factors could predict the response to interferon (IFN) therapy in 55 Japanese patients with chronic hepatitis C. Responses to the IFN therapy were evaluated as sustained response, relapse and non-response by the presence or absence of serum hepatitis C virus (HCV) RNA during the course of treatment and at least 6-months post-treatment. The numbers of sustained response, relapse and non-response were 16 (29.0%), 25 (45.5%) and 14 (25.5%), respectively. Eight out of 16 sustained response cases (50%) showed HCV genotype III. Eight among 10 patients with HCV genotype III (80%) were sustained responders. HCV genotypes were found to be correlated with the response to the IFN therapy (p < 0.0001). None of the histological features, the types of the IFN therapy and other clinical factors showed significant differences. These findings suggest that outcome of the IFN therapy in chronic hepatitis C can be predicted by a virological factor, and that HCV genotype III is a useful predictor of a favorable outcome.
Biopsy↗
Clinical efficacy of fluvastatin for hyperlipidemia in Japanese patients.
The objective of the study was to evaluate the efficacy and safety of fluvastatin in patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia, in a 1-year study (a 12-week open assessment, followed by 40 weeks of active treatment). Of the 337 patients enrolled in the study, the effects of fluvastatin were analyzed in 296 patients at baseline and at 12 weeks. Of these, 265 were receiving 20 mg/day fluvastatin at week 12 and in 20 patients the dose had been increased to 30 mg/day; 11 patients violated the dosing protocol. A total of 229 patients continued into the 40-week, long-term phase, and 212 patients were analyzed at baseline and after 24 and 52 weeks. At the end of treatment, 153 evaluable patients were still taking 20 mg/day fluvastatin, 1 was taking 10 mg/day, and 48 patients were taking 30 mg/day, and 10 were taking 40 mg/day. In the 20 mg/day fluvastatin group, low density lipoprotein cholesterol (LDL-C) levels decreased by 24.1% at week 12 and by 29.3% at week 52. In those patients requiring the higher doses, the corresponding reductions in LDL-C were 20.2% (week 12) and 26.7% (week 52). Total cholesterol was also reduced at week 12 by 17.0% (20 mg/day) and 15.7% (20-30 mg/day), and at week 52 by 20.4% (< or = 20 mg/day) and 19.2% (> or = 30 mg/day). Throughout the study, fluvastatin was generally well tolerated and no serious clinical adverse events were observed. In conclusion, long-term treatment of hypercholesterolemia with fluvastatin at dosages of 20-40 mg daily can be considered both safe and effective.
Anticholesteremic Agents↗
Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated immunity.
The effect of the coating of ovalbumin-reconstituted liposomes with various oligosaccharides on their immunogenicity was investigated in mice. The coating of liposomes with oligomannose or yeast mannan drastically enhanced their ability to induce an ovalbumin-specific delayed-type footpad swelling response with a peak at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those with mannose residue at the nonreducing termini manifested the activity when applied to liposomes. Since such oligosaccharides are ubiquitously found in the body, these results suggested the usefulness of oligomannose-coated liposomes as a safe adjuvant for the induction of cell-mediated immunity.
Adjuvants, Immunologic↗
High fat diet-induced hyperglycemia: prevention by low level expression of a glucose transporter (GLUT4) minigene in transgenic mice.
High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity. To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.
Animals↗
The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells.
In a cultured human hepatoblastoma cell line, Hep G2, chenodeoxycholic acid (CDCA) induced LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold. In contrast, the mRNA levels for mevalonate kinase, farnesyl pyrophosphate synthase and squalene synthase were not changed significantly. The pattern of the induction of the sterol-sensitive genes was similar to the induction by N-acetyl-leucyl-leucyl-norleucinal (ALLN), an SREBP degradation inhibitor, suggesting that CDCA may increase mature SREBPs. CDCA could inhibit the 25-hydroxycholesterol mediated inactivation of SREBP without affecting mRNA levels of SREBPs. These results suggest that CDCA can affect sterol metabolism by a novel mechanism involving the inhibition of the oxysterol-mediated inactivation of SREBP.
Alkyl and Aryl Transferases↗
Expression of an insulin-responsive glucose transporter (GLUT4) minigene in transgenic mice: effect of exercise and role in glucose homeostasis.
The effects of a GLUT4 mini-transgene (containing 7 kb of 5' flanking and 1 kb of 3' flanking sequence and all exons and introns of the GLUT4 gene as well as a small foreign DNA tag) and of exercise training on expression of GLUT4 and glycemic control in mice were investigated. Transgenic mice harboring the minigene expressed < or = 2-fold the normal level of GLUT4 mRNA and protein in skeletal (gastrocnemius) muscle and adipose tissue. This modest tissue-specific increase in GLUT4 expression led to an unexpectedly rapid blood glucose clearance rate following oral glucose administration. In nontransgenic animals exercise caused a 1.5-fold increase in expression of GLUT4 mRNA and protein as well as a significant improvement of glycemic control. In transgenic animals harboring the minigene exercise increased expression of GLUT4 mRNA and protein derived from the minigene and endogenous gene and led to a further improvement of glycemic control. These findings indicate that the cis-regulatory element(s) controlling exercise-induced expression of the GLUT4 gene is located within the nucleotide sequence encompassed by the GLUT4 minigene. The fact that glycemic control is markedly improved by a relatively low level of expression of GLUT4 caused by the transfected minigene and is further enhanced by exercise in transgenic animals demonstrates that GLUT4 plays a pivotal role in glucose homeostasis in vivo. Of the effectors--i.e., cAMP, insulin, and arachidonic acid--known to down-regulate expression of GLUT4 by 3T3-L1 adipocytes in culture, only the decline in circulating arachidonate level in vivo correlated with up-regulation of GLUT4 caused by exercise.
Animals↗