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Biomedical subjects

H Mori

Publications and source records attributed to H Mori.

At least 343 records · Page 19Linked to original sources

Preventive effects of Glycyrrhizae radix extract on estrogen-related endometrial carcinogenesis in mice.

Short- and long-term experiments were conducted to examine the effects of Glycyrrhizae radix (Gl radix) extract on mouse endometrial carcinogenesis. Gl radix treatment (2 weeks) decreased the levels of c-fos/jun mRNA and the corresponding oncoproteins induced by estradiol-17 beta (E2) in castrated mice uteri, as determined by reverse transcription-polymerase chain reaction and Southern blot analysis, and immunohistochemical methods, respectively. For the long-term assays, 98 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body wt.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into four groups as follows: group 1 was given 0.625% Gl radix- and 5 ppm E2-containing diet; group 2, 5 ppm E2-containing diet; group 3, 0.625% Gl radix-containing diet; and group 4, the basal diet alone. Gl radix treatment significantly decreased uterine weights and the incidences of uterine endometrial atypical hyperplastic and malignant lesions. It is suggested that Gl radix has inhibitory effects on E2-related endometrial carcinogenesis in mice, through suppression of estrogen-induced c-fos/jun-expressions.

Animals↗

Beta-catenin (Ctnnb1) gene mutations in diethylnitrosamine (DEN)-induced liver tumors in male F344 rats.

Alterations in multiple phosphorylation sites on exon 3 of the beta-catenin gene have recently been implicated in hepatocarcinogenesis in humans as well as mice. To identify genetic alterations which could be involved in the chemical-induced hepatocarcinogenesis of rats, we analyzed the status of the sites in the beta-catenin gene (Ctnnb1) of liver neoplasms induced by diethylnitrosamine (DEN) in male F344 rats, using the polymerase chain reaction-single strand conformation polymorphism method. In the present investigation, we examined 35 hepatocellular neoplasms (28 adenomas and 7 carcinomas) for the expression of mutations in the region of the beta-catenin gene. Point mutation at codon 32, 35, 37 or 41, which has been reported in human and mouse liver cell carcinomas and/or other cancers, was recognized in eleven (31%) out of 35 lesions (8 adenomas and 3 carcinomas). Our results indicate that Ctnnb1 mutations may contribute to hepatocarcinogenesis in rats. Our finding that Ctnnb1 mutation was present in adenomas as well as carcinomas also suggests that the mutation is a relatively early event in DEN-induced hepatocarcinogenesis in rats.

Adenoma↗

Rates of endometriosis recurrence and pregnancy 1 year after treatment with intranasal buserelin acetate (Suprecur) (a prospective study).

OBJECTIVES: This multicenter prospective study of buserelin acetate (Suprecur) therapy for endometriosis was performed in order to examine pregnancy rates and the recurrence of endometriosis 1 year after the end of intranasal administration. METHODS: This study was conducted at 349 institutions, including university hospitals and major hospitals in Japan, and 1,284 patients were recruited as participants. Recurrence of symptoms was followed for 1 year after the end of administration of buserelin acetate in patients whose condition as a whole was evaluated as "improved" or better at the end of administration. Furthermore, the pregnancy rate was similarly followed in patients who complained of sterility at the commencement of the administration. Recurrence was defined as either a case in which all of the main symptoms observed before administration returned to the pretreatment state, or a case in which at least one symptom deteriorated compared to the pretreatment state. Kaplan-Meier's method was used for statistical analysis. RESULTS: Among 459 patients who could be evaluated for recurrence of symptoms, the cumulative recurrence rate was 17.8% 1 year after the end of administration. Among 156 patients who could be evaluated for pregnancy, the pregnancy rate was 23.3% 1 year after the end of administration. CONCLUSION: Intranasal buserelin acetate therapy exhibited not only transient clinical effects during administration or immediately after the end of administration, but also exhibited specific continuing effects after the end of administration.

Administration, Intranasal↗

Proportion of CD56+3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion.

PROBLEM: The present study investigated the proportion of CD56+3+ T cells in maternal peripheral and decidual lymphocytes in normal pregnancy and spontaneous abortion with and without history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Maternal peripheral blood and decidua were taken from normal pregnancies and missed abortions with and without RSA. Decidual lymphocytes were prepared from decidual tissue and analyzed by flow cytometry. RESULTS: In normal pregnancy, the percentages of CD56+3+ T cells in decidual lymphocytes did not differ from those in the peripheral blood. However, the proportion of CD56+3+ T cells in decidual CD3+ T cells increased higher than that in the peripheral CD3+ T cells. The percentages of decidual CD56+3+ T cells in missed abortions with and without RSA were lower than those in normal pregnancies. CONCLUSION: CD56+3+ T cells may play a role in the maintenance of pregnancy. The phenomenon, where the proportion of CD56+3+ T cells in decidual lymphocytes decreases, may be due to an immunologic event leading to missed abortion.

Abortion, Habitual↗

Decidual natural killer cells in recurrent spontaneous abortion with normal chromosomal content.

PROBLEM: The maternal local immune responses in unexplained recurrent spontaneous abortion (RSA) are not yet well known. Maternal peripheral and decidual natural killer (NK) cells were evaluated in RSA with normal chromosomal content. METHOD OF STUDY: Maternal peripheral blood, villous trophoblast, and decidua were taken from 15 normal pregnancies and 9 RSA patients with normal chromosomes. The NK cells in decidual lymphocytes were evaluated by flow cytometry using monoclonal antibodies for CD56, CD16, and CD3. RESULTS: The percentages of CD56+ CD16- CD3- cells in decidual lymphocytes in RSA were lower than in normal pregnancies (P < 0.002). The CD56+CD16+/CD56+CD16- cells ratio in RSA was higher than in normal pregnancies (P < 0.02). CONCLUSION: The lower percentages of CD56+CD16-CD3- cells in RSA cases may show an inappropriate accumulation of NK cells in the decidua, and this finding may be a factor involved in RSA.

Abortion, Habitual↗

Regiospecific internal desaturation of aliphatic compounds by a mutant Rhodococcus strain.

A mutant Rhodococcus strain lacking the ability to utilize 1-chlorohexadecane was found to cis-desaturate aliphatic compounds, such as 1-chlorohexadecane, n-hexadecane, and heptadecanonitrile, yielding corresponding products with a double bond mainly at the ninth carbon from the terminal methyl groups. A new oxidative pathway involving the cis-desaturation step was suggested for alkane utilization by Rhodococcus spp.

Alkanes↗

Microbial proline 4-hydroxylase screening and gene cloning.

Microbial proline 4-hydroxylases, which hydroxylate free L-proline to trans-4-hydroxy-L-proline, were screened in order to establish an industrial system for biotransformation of L-proline to trans-4-hydroxy-L-proline. Enzyme activities were detected in eight strains, including strains of Dactylosporangium spp. and Amycolatopsis spp. The Dactylosporangium sp. strain RH1 enzyme was partially purified 3,300-fold and was estimated to be a monomer polypeptide with an apparent molecular mass of 31 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Degenerate primers based on the N-terminal amino acid sequence of the 31-kDa polypeptide were synthesized in order to amplify the corresponding 71-bp DNA fragment. A 5.5-kbp DNA fragment was isolated by using the 71-bp fragment labeled with digoxigenin as a probe for a genomic library of Dactylosporangium sp. strain RH1 constructed in Escherichia coli. One of the open reading frames found in the cloned DNA, which encoded a 272-amino-acid polypeptide (molecular mass, 29, 715 daltons), was thought to be a proline 4-hydroxylase gene. The gene was expressed in E. coli as a fused protein with the N-terminal 34 amino acids of the beta-galactosidase alpha-fragment. The E. coli recombinant exhibited proline 4-hydroxylase activity that was 13. 6-fold higher than the activity in the original strain, Dactylosporangium sp. strain RH1. No homology was detected with other 2-oxoglutarate-dependent dioxygenases when databases were searched; however, the histidine motif conserved in 2-oxoglutarate-dependent dioxygenases was found in the gene.

Actinomycetales↗

Synchrotron microangiography reveals configurational changes and to-and-fro flow in intramyocardial vessels.

In 8 dogs, in situ microangiography using synchrotron radiation visualized penetrating transmural arteries (PTAs) with a diameter of >60 micrometers and allowed quantitation of vessel diameters of >140 micrometers. Myocardial contraction reduced the vascular short-axial diameters to 87 +/- 17% (n = 62, P < 0.001, paired t-test) of the end-diastolic values and increased the longitudinal dimension to 129 +/- 5% (n = 45, P < 0.001). The diameter reduction in the subendocardial PTA segments was significantly more marked than that in the subepicardial PTA segments (60 +/- 12 vs. 88 +/- 12%, n=13, P < 0.001, paired t-test). Intracoronary administration of dobutamine (0.1 micrograms. kg-1. min-1) increased, and in contrast, partial clamping of the coronary artery (ischemia) decreased, the configurational changes. To-and-fro blood flow was clearly observed in PTAs with visual identification of capacitive backflow, resistive forward flow during ischemia on coronary arteriography, and even under baseline conditions in coronary venography. Thus this method advances our understanding of mechanical influences on the coronary circulation.

Animals↗

Branching patterns of intramural coronary vessels determined by microangiography using synchrotron radiation.

The intramural coronary artery (IMCA) with a diameter of 50-500 micrometers is critical for blood supply to the inner layers of heart muscle. We introduced digital measurement to microangiography using monochromatic synchrotron radiation and quantified branching patterns of the IMCA, the epicardial coronary artery (EPCA), and the distal ileal artery (DIA). The pre- and postbranching diameters were measured (95-1,275 micrometers) in seven dogs. A typical arterial segment divided into two nearly equivalent branches, and a regression line of daughter-to-mother diameter plots was almost identical among the EPCA (y = 0.838x - 16.7 in micrometers), IMCA (y = 0.737x - 2.18), and DIA (y = 0.755x + 8.63). However, a considerable difference was present at a segment where a proximal IMCA branched off from an EPCA (y = 0.182x + 90.2). Moreover, a proximal IMCA diameter had no relationship to the branching order from an EPCA. The precision of this method was confirmed by the good correlation of diameter measurements between two independent observers (r = 0.999, y = 1.02x - 1.07). In conclusion, using digital microangiography we demonstrated that the self-similar branching pattern of coronary arteries was discrete at the connection between the IMCA and EPCA.

Angiography↗

Intramyocardial vascular volume distribution studied by synchrotron radiation-excited X-ray fluorescence.

We evaluated the vascular volume distribution with fine resolution (0.1-1.3 mg myocardial tissue) in the sagittal plane of the left ventricle by using the microsphere filling method in 21 dogs. The coronary arterial volume density in the sagittal plane did not exhibit normal distribution and was characterized by variability among the outer-to-inner layers and within the layers (+2SD/-2SD > 80 times), and the median values in the layers ranged from 4.7 to 22. 9 nl/mg myocardial tissue. The fractal analysis of vascular volume revealed a self-similar nature with a fractal dimension (D value) similar to that of flow distribution (1.20 +/- 0.05 and 1.24 +/- 0. 09 for vascular volume and flow distribution, respectively) and had a more marked variability than the flow. The correlation of the regional vascular volume between adjacent regions decreased as the distance increased. However, the correlation coefficients in the endocardial-to-epicardial direction were significantly higher than those in the anterior-to-posterior direction (P < 0.05 by paired t-test). In conclusion, we determined intramyocardial vascular volume density in the sagittal plane, and the distribution revealed considerable variability, self-similarity, and asymmetry in the correlation among the adjacent regions. These observations could be related to the characteristics of the intramural coronary vascular network.

Animals↗

Characterization of human immunodeficiency virus type 1 resistant to modified cyclodextrin sulphate (mCDS71) in vitro.

Drug resistance of human immunodeficiency virus type 1 (HIV) to modified cyclodextrin sulphate (mCDS71) has been analysed with respect to both the in vitro appearance of resistance to the compound and the mechanism of the acquisition of resistance. Resistant strains could be obtained in all three strains (NL432, KK-1 and A018) tested after serial passages in MT-4 cells with a gradual increase of the concentration of mCDS71. Cross-resistance both to mCDS71 and dextran sulphate 8000 was observed. As a result of sequencing analysis of the gp120 V3-C5 region of resistant strains, the mechanism of resistance can be explained in several ways: (i) substitution of sugar chain-binding amino acids, N and S; (ii) three to five amino acid deletion in V4 loop; and (iii) several mutations in V3 and V4 regions. The real cause of the resistance may be a combination of these three mechanisms. The results suggest that the target of mCDS71 is relatively widely distributed on the viral surface glycoprotein.

Amino Acid Sequence↗

The effect of feeding carrots on immunoglobulin E production and anaphylactic response in mice.

Carrot juice was administered orally to BALB/c mice immunized intraperitoneally with dinitrophenylated (DNP)-OVA for about 1 month. The titers of DNP-specific IgE, DNP-specific IgG, and the levels of total IgE in mouse sera were determined. The DNP-specific IgE production by mice fed carrot juice was significantly inhibited. On the other hand, the DNP-specific IgG production and the level of total IgE in mice fed carrot juice were not significantly different from those in control mice. We also examined the effect of feeding carrots on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed carrots swelled less than those of control mice. Furthermore, the rise in serum histamine in the mice fed carrots under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with DNP-OVA in vitro. The spleen cells from the mice fed carrots produced more interferon-gamma than those from the control group. In contrast, the spleen cells from the mice fed carrots produced less interleukin-4 than those from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed carrots was also higher than that of the control group. These findings suggest that feeding carrots improves the helper T cell (Th)1/Th2 balance, inhibiting specific IgE production and antigen-induced anaphylactic response.

Anaphylaxis↗

Improvement by 5-amino-4-imidazole carboxamide riboside of the contractile dysfunction that follows brief periods of ischemia through increases in ecto-5-nucleotidase activity and adenosine release in canine hearts.

5-Amino-4-imidazole carboxamide (AICA) riboside increases adenosine release in ischemic myocardium, suggesting that AICA riboside improves contractile dysfunction. In 49 open-chest dogs, contractile function assessed by fractional shortening (FS) was observed 3 h after the onset of reperfusion following 15 min of occlusion of the left anterior descending coronary artery. During reperfusion, the treatment with AICA riboside increased adenosine concentration in the coronary venous blood (536+/-44 vs. 281+/-21 pmol/ml at 3 min of reperfusion, p<0.001) and peak coronary hyperemic flow (367+/-13 vs. 300+/-21 ml/100 g per min, p<0.001) when compared with the untreated group. FS at 3h of reperfusion increased in the AICA riboside group (21.1+/-2.3 vs. 12.8+/-0.6% in the untreated group, p<0.001). AICA riboside increased myocardial ecto-5'-nucleotidase activity. Administration of adenosine also augmented coronary hyperemic flow and increased FS to the levels of the AICA riboside group. Either 8-phenyltheophylline (an antagonist of adenosine receptors) or alpha,beta-methylene-adenosine 5'-diphosphate (an inhibitor of ecto-5'-nucleotidase) completely abolished the increased coronary hyperemic flow and improvements of myocardial contractile function due to AICA riboside. Thus it was concluded that AICA riboside improves the contractile dysfunction that follows a brief period of ischemia via adenosine-dependent mechanisms.

5'-Nucleotidase↗

The telomerase activities in several organs and strains of rats with ageing.

Telomerase activity is known to be implicated both in cell immortalization and carcinogenesis. Telomerase activity has not been detected in most human somatic tissues. However, we previously confirmed that the activity is present both in methylazoxymethanol acetate-induced rat colonic adenocarcinoma and non-treated colonic mucosa, presumably indicating the tissue-specific activity of the enzyme in rats. To determine the standard activity of rat telomerase in various organs in relation to differences in sex, age and strain, we examined the activity by using the telomeric repeat amplification protocol (TRAP) assay. The testis, liver, and colon mucosa showed the activity. The brain had very low or negative activity in 5-week-old male rats of the F344, SD, Wistar, Donryu or ACI strains. Age (5-week-old and 9-month-old) or sex difference for the activity was not apparent in rats of these strains. In general, telomerase activity in the fetal brain, liver and kidney was stronger than in the adult organ. The telomerase activity of each organ was different from that of human. This difference may indicate that the rat has a specific mechanism for maintaining the telomeric repeats of the chromosome even in somatic tissues. The basic information resulting from this study may be useful for the study of the role of telomerase in tumorigenesis in animal experiment models.

Aging↗

Molecular cloning of isomaltotrio-dextranase gene from Brevibacterium fuscum var. dextranlyticum strain 0407 and its expression in Escherichia coli.

The gene encoding an extracellular isomaltotrio-dextranase (IMTD), designed dexT, was cloned from the chromosomal DNA of Brevibacterium fuscum var. dextranlyticum strain 0407, and expressed in Escherichia coli. A single open reading frame consisting of 1923 base pairs that encoded a polypeptide composed of a signal peptide of 37 amino acids and a mature protein of 604 amino acids (M(r), 68,300) was found. The primary structure had no significant similarity with the structure of two other reported exo-type dextranases (glucodextranase and isomalto-dextranase), but had high similarity with that of an endo-dextranase isolated from Arthrobacter sp. Transformed E. coli cells carrying the gene encoding mature protein of IMTD overproduced IMTD under the control of the T7 phage promoter induced by IPTG. The purified recombinant enzyme showed the same optimum pH, lower specific activity, and similar hydrolytic pattern, as to those of native IMTD.

Amino Acid Sequence↗

HIV-1 protease inhibition and anti-HIV effect of natural and synthetic water-soluble lignin-like substances.

Water-soluble lignin extracted from natural sources and dehydrogenated polymers of p-coumaric acid and ferulic acid inhibited HIV-1 protease activity. The dehydrogenated polymers, which are thought to be model compounds for lignin, were synthesized and fractionated into four ranges of molecular mass by ultra-filtration: i.e., over 30 kDa, 30-10 kDa, 10-1 kDa and 1 kDa-500 Da. All of these fractions had HIV-1 protease inhibitory activity. The anti-HIV-1 effect of the smallest mass fractions of the dehydrogenated polymers (1 kDa-500 Da) was also tested, and it was found that these fractions inhibited the replication of HIV-1 in MT-4 cells.

Cell Line↗

Influences of long-term administration of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, in rats.

In order to examine the influences by long-term feeding of 24R, 25 dihydroxyvitamin D3[24R, 25(OH)2D3], an active form of vitamin D, Wistar rats (14-week-old, male, 20 rats/group) were fed a powder diet containing 0 or 5 ppm 24R, 25(OH)2D3 for 57 weeks. Final body weights and total food consumption were comparable between the groups. Urinary calcium levels were significantly (p < 0.05 or 0.01) increased by the administration of 24R, 25(OH)2D3 at weeks 3, 22 and 56, although the levels of serum calcium did not differ between the groups at the termination of week 57. In the 24R, 25(OH)2D3 group, weights of the adrenals and femurs were significantly (p < 0.01) increased. Histopathologically, this was found due to thickening of cortical bone in the femurs, and medullary hyperplasia and pheochromocytoma of the adrenals. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-labeling indices for intact adrenal medulla, medullary hyperplasia and pheochromocytoma in the 24R, 25(OH)2D3 group were respectively 1.82 +/- 1.21, 5.88 +/- 4.13 and 16, all higher than that for the adrenal medulla in the control group (0.87 +/- 0.67). These results indicate that 24R, 25(OH)2D3 at a dose with which serum calcium is not chronically increased causes thickening of the cortex of the femur, and development of adrenal proliferative lesions, suggesting that rats may be too sensitive for results to be relevant to human risk assessment.

24,25-Dihydroxyvitamin D 3↗

Suppressive effects of chlorogenic acid on N-methyl-N-nitrosourea-induced glandular stomach carcinogenesis in male F344 rats.

The modifying effects of chlorogenic acid (CA) on N-methyl-N-nitrosourea (MNU)-induced glandular stomach carcinogenesis were investigated in five groups of male F344 rats. Rats in Groups 1 through 3 were given MNU in drinking water at a concentration of 400 ppm for 12 weeks. Animals of Group 1 were then kept on the basal diet alone, and those of Group 2 or 3 were fed a diet containing 500 or 250 ppm CA for a subsequent 22 weeks. Group 4 was exposed to CA alone through the experimental period (36 weeks), and Group 5 was given the basal diet continuously and treated as a control. At the end of the experiment, the incidence of glandular stomach carcinoma of Group 3 was significantly smaller than that of Group 1 (p < 0.03). The incidence of adenomatous hyperplasia of Group 2 was also significantly lower than that of Group 1 (p < 0.02). In addition, the proliferating cell nuclear antigen (PCNA) labeling index of the epithelial cells from the non-neoplastic mucosa in rats of Group 2 or 3 was significantly smaller than that of Group 1 (p < 0.0001). These results suggest that CA has a chemopreventive effect on MNU-induced rat glandular stomach carcinogenesis by exposure during the post-initiation phase, and CA may be a promising agent for prevention of human stomach cancer.

Animals↗