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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 307 records · Page 17Linked to original sources

Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves): 2. Suppressing effect of Tochu tea on the urine mutagenicity after ingestion of raw fish and cooked beef.

The effect of Tochu tea, which is an aqueous extract of Eucommia ulmoides leaves and a popular-beverage in Japan, on the urine mutagenicity before and after ingestion of raw fish and cooked beef was studied using Salmonella typhimurium YG1024. Urines were collected from seven healthy, non-smoking Japanese women before and after ingestion of raw fish and cooked beef. In experiment 1,3 were in a control group and 4 were in a Tochu tea-drinking group (2000 ml per day). The mutagenicity of urine from the Tochu tea-drinking group was much lower. In experiment 2 the 7 women switched groups; the tea-drinking group became the control group, and the control group became the Tochu tea-drinking group. Again, the mutagenicity of urine collected from the Tochu tea-drinking group was much lower. These results suggest that the decrease in the mutagenicity of the urine from the Tochu tea-drinking group was due to the intake of Tochu tea, but not to individual differences. Thus, the ingestion of Tochu tea may reduce human exposure to dietary mutagens.

Adult↗

Lipoprotein analyses in patients with stable angina and acute coronary syndrome.

We have performed lipid analyses by using a table-top ultracentrifuge based on the Hatch and Lees' method in 77 subjects (60 men, 17 women: mean age, 63 years) to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects had coronary artery disease and 13 normal subjects were controls. They were divided into the groups with stable angina pectoris and with unstable angina pectoris or acute myocardial infarction (acute coronary syndromes). In patients with coronary artery disease, there were no significant differences from control in age, body mass index, total cholesterol, however, HDL cholesterol was significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio, which is thought to reflect the size of LDL in coronary artery disease, was significantly smaller than that in the controls; mean values were 1.2 in coronary artery disease and 1.4 in controls. There were no significant differences in those lipoprotein disorders between the patients with stable angina and those with acute coronary syndromes. Though these lipoprotein abnormalities would not play a trigger role in acute coronary syndrome, they are characteristic of the lipid profile of patients with coronary artery disease.

Aged↗

Microsatellite instability in in situ and invasive sporadic breast cancers of Japanese women.

We studied the timing of microsatellite instability (referred to as replication error; RER) presentation during human breast carcinogenesis using tissue microdissected from both in situ and invasive breast cancers of Japanese women. We analyzed 100 breast cancer specimens for RER at nine genomic loci on seven chromosomes. Eight of the 100 cases (8%) were RER-positive at one or more chromosomal loci. Additionally; we obtained genomic DNA from two of four RER-positive patients with an intraductal component, both of which showed microsatellite instability in in situ foci. This finding indicates that microsatellite instability may be an early event during human breast carcinogenesis.

Breast Neoplasms↗

Microsatellite instability in sporadic human breast cancers.

Human breast-cancer specimens from 100 patients were analyzed for microsatellite instability (referred to as replication error; RER) at 12 genomic loci on 7 chromosomes, and results were correlated with clinicopathologic characteristics. In 42 of 100 breast-cancer patients, we investigated whether RER was associated with the amplification of oncogenes and/or suppression of tumor-suppressor genes. Of the 100 patients, 8 (8%) were RER-positive at one or more chromosomal loci. The majority of RER-positive patients had early-stage disease with ER-positive tumors, suggesting that RER occurs early in breast tumorigenesis. However, no significant correlation was observed between RER and oncogenes or tumor-suppressor genes. Thus, the mechanism of RER in sporadic human breast cancer may be independent of the multi-step carcinogenesis caused by the alterations of oncogenes and tumor-suppressor genes.

Breast Neoplasms↗

Tea polyphenols as inhibitors of mutagenicity of major classes of carcinogens.

Previous research suggested that the mutagenicity of some genotoxic carcinogens, mainly heterocyclic amines, was decreased by green or black tea extracts, or tea polyphenol fractions. Thus, it seemed important to test a variety of genotoxic carcinogens with distinct chemical structures and means of biochemical activation as regards modification of mutagenicity in appropriate strains of Salmonella typhimurium by 3 concentrations of polyphenols 60, 100, or B, standard commercial polyphenol preparations from green or black tea. Polyphenols sharply decreased the mutagenicity of a number of aryl- and heterocyclic amines, of aflatoxin B1, benzo[a]pyrene, 1,2-dibromoethane, and more selectively, of 2-nitropropane, all involving an induced rat liver S9 fraction. Good inhibition was found with 2 nitrosamines that required a hamster S9 fraction for biochemical activation. No effect was found with 1-nitropyrene, and with the direct-acting (no S9) 2-chloro-4-methyl-thiobutanoic acid. Thus, with some exceptions, polyphenols considerably decreased the mutagenicity of diverse types of carcinogens.

Amines↗

Effect of topical application of a stable prostacyclin analogue, SM-10902 on wound healing in diabetic mice.

The mechanism of wound healing induced by topical application of an ointment containing a new stable prostacyclin analogue, SM-10902 ((+)-methyl[2-[(2R,3aS,4R,5R, 6aS)-octahydro-5-hydroxy-4-[(E)-(3S,5S)-3-hydroxy-5-methyl-1- nonenyl]-2-pentalenyl] ethoxy] acetate), was investigated in the full-thickness wounds of genetically diabetic mice (db/db mice). The db/db mice treated with SM-10902 ointment (1, 10 and 100 micrograms/g) showed greater decrease in wound lesion area not covered with epidermis and fewer complete healing days than those treated with ointment base, and the effects of this prostacyclin analogue were greater than those of lysozyme chloride ointment (50 mg/g, Reflap ointment). SM-10902 ointment increased skin blood flow in the central site of the wound with development of wound healing. Histological evaluation of wounds revealed that SM-10902 ointment increased the capillary number during the early stage of the wound-healing process. These results suggest that SM-10902 ointment promotes wound healing through the stimulation of angiogenesis and the improvement of blood flow in neovascularization of repairing wound and may be useful in the treatment of skin ulcers caused by peripheral circulatory insufficiency.

Administration, Topical↗

Effects of prostaglandins and cyclic AMP on cytokine production in rat leukocytes.

Prostaglandins E1, prostaglandin E2, 3-oxa-methano-prostaglandin I1 (SM-10906), a stable prostaglandin I2 analog, and dibutyryl cyclic AMP suppressed the production of tumor necrosis factor and interleukin-1 in lipopolysaccharide-stimulated rat pleural resident monocytic cells, whereas they enhanced the production of interleukin-6 and cytokine-induced neutrophil chemoattractant (CINC), a rat interleukin-8-like chemokine, in these cells. SM-10906 also inhibited the in vivo production of tumor necrosis factor and interleukin-1 in pleural exudates, when injected into the rat pleural cavity concomitantly with carrageenin. The cyclic AMP (cAMP) level in the lipopolysaccharide-stimulated resident cells was increased when the cells were incubated in the presence of prostaglandin E1, prostaglandin E2 or SM-10906. Prostaglandin I2 showed only slight effects. The addition of pentoxifylline, a phosphodiesterase inhibitor, to the incubation mixture increased the cAMP level and also enhanced the effect of prostaglandins, indicating that these regulating actions of prostaglandins may be exerted partly through a mechanism involving an increased intracellular cAMP level.

Alprostadil↗

The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

Adrenal Cortex↗

Enhancement of bone formation by drawn poly(L-lactide).

Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.

Animals↗

Effects of calcium in continuous cardioplegia on myocardial protection.

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca (0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37 degrees C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1 +/- 2.9%, 80.6 +/- 2.0%, and 71.5 +/- 3.7% (mean +/- SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.

Animals↗

A study of malabsorption in pancreatic cancer.

The type, incidence, and severity of malabsorption in patients with pancreatic cancer were investigated. The following absorption tests were performed; pancreatic function diagnostant (PFD) test, measurement of serum carotene levels, and 5 g D-xylose absorption test. Rates of abnormality in the tests were 75.7% of 37, 54.2% of 48, and 54% of 50 patients with pancreatic cancer, respectively. In particular, a marked decrease of values in the xylose absorption test was characteristic and more often recognized in patients with carcinoma of the pancreas with occlusion of the superior mesenteric vein. The presence of malabsorption (disturbed transport through the portal vein), in addition to maldigestion of nutrients, is suggested to induce severe malnutrition in patients with pancreatic cancer.

Adult↗

Antithrombotic effect of topically applied 3-oxa-methano-prostaglandin I1 in the microcirculation and antiplatelet functions of its active form.

The antithrombotic effect of topical application of the 3-oxa-methano-prostaglandin (PG) I1 analog, SM-10902 in the microcirculation and in vitro antiplatelet functions of its active form SM-10906 were estimated in comparison with PGI2 and PGE1. In rat platelets, SM-10906 evoked accumulation of intracellular cyclic adenosine 3',5'-monophosphate, and exhibited antiaggregatory and disaggregatory activities, which were all enhanced by the phosphodiesterase inhibitor theophylline. Additionally, SM-10906 was shown to inhibit platelet adhesion to collagen in human platelet-rich plasma. PGI2 and PGE1 also showed in vitro antiplatelet effects in the order of PGI2 > SM-10906 > or = PGE1. SM-10902 exhibited a dose-dependent anti-thrombotic effect in the guinea pig mesenteric arteriole by a topical application, and this activity might be exerted by the antiplatelet functions of SM-10906. Although SM-10906, PGI2 and PGE1 also showed the antithrombotic effects, SM-10902 was the most potent. In conclusion, the present studies indicate that an external topical preparation of SM-10902 may be useful for the therapy of peripheral circulatory insufficiency.

3',5'-Cyclic-AMP Phosphodiesterases↗

Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical.

The scavenging effects of tea catechins and their epimerized, acylated, and glucostylated derivatives on 1,1-diphenyl-2-picrythydrazyl (DPPH) radical were evaluated by electron spin resonance spectrometry. Tea catechins and their epimers were shown to have 50% radical scavenging ability in the concentration range of 1 to 3 microM. No significant differences were observed between the scavenging activities of tea catechins and their epimers, and, hence, the scavenging effects of catechins are not dependent on their sterical structure. The relationship between scavenging ability and the structure of tea catechins was also examined with acylated and glucosylated catechin derivatives. It is suggested that the galloyl moiety attached to flavan-3-ol at 3 position has a strong scavenging ability on the DPPH radical as well as the ortho-trihydroxyl group in the B ring, which elevates the radical scavenging efficiency above that of the ortho-dihydroxyl group; as has been recognized in other flavonoids such as flavones. The results obtained from the reactivity of tea catechins with the DPPH radical at different pHs suggest not only that the ortho-trihydroxyl group and the galloyl moiety contribute to maintaining the DPPH radical scavenging ability more effectively in a wide range of conditions from acidic to alkaline, but also that the radical scavenging efficiency of the ortho-dihydroxyls in the B ring is limited in neutral to alkaline regions. The difference between the scavenging abilities of the trihydroxyls (probably in the galloyl moiety) and the dihydroxyls can be explained in terms of redox potentials. It is concluded that the ortho-trihydroxyl group in the B ring and the galloyl moiety at 3 position of flavan-3-ol skeleton are the most important structural features for displaying an excellent scavenging ability on the DPPH radical.

Bepridil↗

Indocyanine green angiographic findings in Vogt-Koyanagi-Harada disease.

PURPOSE: To report the indocyanine green angiographic findings associated with Vogt-Koyanagi-Harada disease and compare them with fluorescein angiographic findings and monochromatic scanning laser images. METHODS: In a prospective study, indocyanine green angiography, by scanning laser ophthalmoscopy or infrared fundus photography, was performed in ten consecutive patients (20 eyes) with Vogt-Koyanagi-Harada disease during the acute stage before and recovery stage after corticosteroid treatment. Findings were compared with fluorescein angiographic features and monochromatic scanning laser imaging. RESULTS: During the acute stage of the disease, indocyanine green angiography disclosed a dark background in the early phase and multiple, non-uniform hypofluorescent lesions in the midphases. Lesions were more numerous and extensive than areas either of serous retinal detachment on monochromatic scanning laser imaging or of punctate hyperfluorescence on fluorescein angiography. During the recovery stage, the abnormal dark background on indocyanine green angiography at initial examination resolved, with choroidal vessels visible in all cases, but nonuniform hypofluorescent lesions persisted in most eyes. Fluorescein angiography disclosed hypofluorescent patchy areas, and confocal infrared laser imaging showed some bright reflective lesions in three patients with especially severe clinical symptoms. On final examination after an average of 17.7 months, both angiographies still disclosed abnormal findings in these three patients. CONCLUSIONS: Indocyanine green angiographic findings suggest that choroidal inflammation may cause a transient choroidal circulatory disturbance during the acute stage of Vogt-Koyanagi-Harada disease. In more severe cases, this dysfunction may secondarily damage the retinal pigment epithelium.

Acute Disease↗

Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects.

This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.

Blood Glucose↗

Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures.

Taxus cell culture may be an alternative source of paclitaxel and related taxane production. Significantly increased amounts of paclitaxel and baccatin III were observed in cultured cells of Taxus species after exposure to methyl jasmonate. Among the three species of Taxus tested, Taxus media showed the highest paclitaxel content while Taxus baccata showed the highest baccatin III content when 100 microM of methyl jasmonate was added to the culture media. Furthermore, the activities of methyl jasmonate and related substances for inducing paclitaxel production were compared in cell suspension cultures of T. media. Methyl jasmonate and its free acid showed the strongest promoting activity. Reduction of the keto group at the C-3 position greatly reduced this activity. cis-Jasmone, which does not have a carboxyl group at the C-1 position, had almost no activity. These results suggest that these two regions of methyl jasmonate are important for promoting the production of paclitaxel and related taxanes in Taxus cell cultures.

Acetates↗

Specificity of glossopharyngeal nerve responses to astringent compounds in Xenopus.

Astringent compounds were applied to oral epithelium of the clawed toad, Xenopus laevis, and rapidly rising and highly sensitive responses could be recorded from the whole glossopharyngeal nerve, but not at all from the trigeminal nerve. The response to 10 mM tannic acid decreased progressively with repetitive application. These responses to tannic acid, however, recovered completely by treating with chemicals capable of forming strong hydrogen and hydrophobic bonds. These chemical bondings are generally recognized as a model for polyphenol (tannin)-protein interactions based on physico-chemical measurements in vitro. The high affinities of these chemicals for tannic acid may be effective in releasing both bonds in the interaction of tannic acid with the receptor molecules. Our results provide in vivo evidence for this model.

Animals↗

The effect of postoperative analgesia with continuous epidural bupivacaine after cesarean section on the amount of breast feeding and infant weight gain.

The purpose of this study is to determine the effect of postoperative analgesia on the amount of breast feeding and infant weight gain. Thirty parturients undergoing elective cesarean section under spinal anesthesia were randomly allocated to receive postoperative pain management with (S-E group, n = 15) or without epidural bupivacaine (S group, n = 15). Epidural analgesia was performed for 3 days with a continuous epidural infusion (0.7 mL/h) of 0.25% bupivacaine. Diclofenac was available on demand in all patients. The weight of milk fed by breast and the infant weight were measured for 11 days after cesarean section. In the S-E group, the visual analog pain score after surgery was significantly lower and both the weight of milk fed by breast and the infant weight during the study were significantly more than the respective values in the S group. The S group required a larger dose of diclofenac after the operation than did the S-E group. We suggest that satisfactory postoperative pain relief with continuous epidural bupivacaine for 3 days after cesarean section improved the amount of breast feeding and the gain of infant weight.

Adult↗