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Biomedical subjects

K Akimoto

Publications and source records attributed to K Akimoto.

At least 109 records · Page 6Linked to original sources

Antihypertensive effect of sesamin. II. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy.

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using two-kidney, one-clip (2K,1C) renal hypertensive rats. After clipping the left renal artery, animals were assigned to either a normal diet group (control group) or a sesamin-containing (1% (w/w)) diet group (sesamin group). The sham-operated rats (sham group) were fed a normal diet and tap water. The systolic blood pressure of the control group increased progressively in comparison with the sham group. This 2K,1C-induced hypertension was markedly reduced by feeding the sesamin-containing diet. The systolic blood pressure after 4 weeks was 123.60 +/- 4.01 mmHg in the sham group, 187.43 +/- 5.69 mmHg in the control group and 145.57 +/- 6.78 mmHg in the sesamin group, respectively. There were significant increases in left ventricle plus septum weight-body weight ratio in the control group compared with the sham group. This rise was also significantly reduced in the sesamin group. When the thoracic aorta was histochemically evaluated, the wall thickness and wall-to-lumen ratio in the control group were significantly increased, compared with the sham group, indicating that vascular hypertrophy had occurred in the control group. The sesamin diet tended to ameliorate this vascular hypertrophy, although its effect was not statistically significant. These findings suggest that sesamin is useful as prophylactic treatment to combat the development of renal hypertension and cardiac hypertrophy.

Animals↗

Immunostimulatory and antitumor activities of monoglycosylceramides having various sugar moieties.

Ten kinds of monoglycosylceramides (MonoCers), having the same ceramide portion and different sugar moieties, were synthesized and their immunostimulatory and antitumor activities were examined. The manner of combination between sugar and ceramide has been demonstrated to affect the manifestation of immunostimulatory and resultant antitumor activities of MonoCers, and in the case of D-MonoCers having the D-sugar, alpha-D-MonoCers (sugar combined to ceramide in an alpha-configuration) show stronger activities than beta-D-MonoCers. Furthermore, the form of sugar, not the furanose-form but the pyranose-form, and the 2"- and 4"-hydroxyl groups of the pyranose-form of sugar, seemed to play an important role in the manifestation of the activities of alpha-D-MonoCers.

Adjuvants, Immunologic↗

[Angles among main cranial sutures in Japanese].

To examine a relation of angles among the coronal, sagittal and lambdoid sutures to the size of the calvaria as well as to the remains of the metopic suture, 158 adult Japanese calvae or calottes were observed. The calvae used consisted of four groups: group M composed of 74 male calvae without the metopic suture; group F, of 41 female calvae without the same suture; group Un, of 27 sex-unknown calvae without the same suture; and group Um, of 16 sex-unknown calvae with the same suture. The angles among the sutures were measured at both bregma and lambda. The size of the calvaria was represented by bistephanic arc and breadth (distance between the stephanions), and by parietal sagittal arc and chord (distance from the bregma to the lambda). Results obtained were as follows. The distances both between the stephanions and from the bregma to the lambda were larger in M than in F, though these distances in M, F and Un were much the same as those in Um. The bistephanic index (breadth/arc) was higher in Um than in F, whereas the sagittal parietal indices (arc/chrod) in M, F and Um were similar to one another. Apical angle of the frontal squama was larger in M than in F, and was larger in Um than in M and F. However, apical angle of the occipital squama showed no difference among M, F and Um.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗

Pharmacokinetics and pharmacodynamics of the tulobuterol patch, HN-078, in childhood asthma.

BACKGROUND: Recently, a novel percutaneous adhesive tulobuterol preparation, HN-078, has been developed and tests using healthy adult subjects have indicated it to be effective for controlling exacerbations early in the morning if applied at bedtime. In children, percutaneous application is very important to eliminate side effects, including abdominal pain and appetite loss. OBJECTIVE: We report the pharmacokinetics and pharmacodynamics of tulobuterol patch, HN-078, in the treatment of childhood asthma. METHODS: Single applications of HN-078 were applied transdermally in six children with asthma who had been admitted to a hospital. Subjects weighing less than 30 kg received 1 mg of tulobuterol while subjects weighing 30 kg or above received 2 mg on the chest for 24 hours. Serum tulobuterol levels and peak expiratory flow rate were determined before and after each application. RESULTS: Cmax of tulobuterol was determined to be 1.33 +/- 0.21 ng/mL, Tmax was 14.0 +/- 2.0 hours, and AUCO-t was 27.1 +/- 4.2 ng.hr/mL. These pharmacokinetic parameters per body surface area of children were nearly equivalent to those of adults obtained in other studies. Peak expiratory flow rate values obtained after application of HN-078 significantly increased in comparison to those obtained before application. No significant changes were observed in pulse rate or blood pressure, and no side effects were found with regard to the subjective symptoms and skin conditions. CONCLUSIONS: These results suggest that the patch formulation of tulobuterol, HN-078, will be very useful for the treatment of pediatric asthma. It is especially significant that no side effects were observed.

Administration, Cutaneous↗

alpha-Tocopherol enhances the hypocholesterolemic action of sesamin in rats.

The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.

Animals↗

Activation of novel protein kinases C delta and C epsilon upon mitogenic stimulation of quiescent rat 3Y1 fibroblasts.

Rat fibroblast 3Y1 cells express at least three protein kinase C species, conventional PKC alpha (cPKC alpha), novel PKC delta (nPKC delta), and novel PKC epsilon (nPKC epsilon). The stimulation of quiescent 3Y1 cells by serum (or epidermal growth factor (EGF) but not 12-O-tetradecanoylphorbol-13-acetate (TPA) results in the induction of DNA synthesis. Upon stimulation by serum or EGF, endogenous PKC species showed no indication of activation such as translocation or down-regulation, whereas TPA or synthetic diacylglycerol caused activation of all these PKC species when judged by these criteria. The only indication of activation observed upon serum or EGF stimulation was an upward shift in the electrophoretic mobility of nPKC delta. The phosphorylation levels of endogenous PKC members determined by in vivo metabolic labeling experiments revealed increased phosphorylation of both nPKC delta and nPKC epsilon, but only a slight increase for cPKC alpha in response to serum or EGF. On the other hand, TPA caused increased phosphorylation of all three PKC species. Overexpression of these PKC members by introduction of the corresponding cDNA expression plasmids resulted in the enhancement of the cell response to TPA when monitored in terms of transcriptional activation through TPA- or serum-responsive elements. Such enhancement in transcriptional activation by overexpression of cPKC alpha, nPKC delta, or nPKC epsilon was also observed in response to diacylglycerol, indicating that all these PKC species are activated by diacylglycerol in cells. In contrast to these nonphysiological stimuli, serum (or EGF) stimulation of 3Y1 cells that overexpress the respective PKC members revealed a clear difference between cPKC and nPKC, in that overexpression of nPKC delta or nPKC epsilon resulted in a large increase in TPA- or serum-responsive element activation, whereas the overexpression of cPKC alpha increased activation only very slightly. These results indicate that the mitogenic stimulation of quiescent 3Y1 cells results in selective activation of endogenous nPKC members and that the modes of activation of cPKC and nPKC differ from each other.

Animals↗

A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells.

Protein kinase C (PKC)-related cDNA clones isolated from cDNA libraries of mouse P19 embryonal carcinoma cells and mouse brain encoded a 67-kDa protein, PKC lambda. PKC lambda shows the highest amino acid sequence identity with PKC zeta (72%), the third class of the PKC family. Northern blot analysis showed that the mRNA for PKC lambda is expressed in a wide variety of cells and tissues, including P19 and NIH 3T3 cells, as well as brain, kidney, testis, and ovary. In undifferentiated P19 cells, the mRNA for PKC lambda is the most abundant among all the PKC family members. The differentiation of P19 cells results in an increase in PKC alpha and epsilon, and a decrease in PKC lambda. Antiserum raised against a peptide of PKC lambda identified a 74-kDa protein in P19 cell extracts as well as in extracts from COS cells transfected with the PKC lambda expression plasmid. Autophosphorylation of the PKC lambda that immunoprecipitated with the specific antiserum was observed, indicating that PKC lambda possesses protein kinase activity. A phorbol ester binding assay using intact COS cells expressing PKC lambda failed to detect binding activity specific to PKC lambda at phorbol dibutylate concentrations up to 300 nM, suggesting that PKC lambda does not possess phorbol ester binding activity. These results, in conjunction with the results obtained in parallel experiments with PKC zeta and other PKC members, suggest a biochemical similarity between PKC lambda and zeta and their clear difference from other PKC members.

Amino Acid Sequence↗

Regional analysis of ceramides within the stratum corneum in relation to seasonal changes.

We studied the regional variations and seasonal changes of ceramide quantities in the stratum corneum of human skin. In summer, the total lipid amounts extracted from the stripped stratum corneum were highest in the forehead, followed by the chest and upper back, with the lowest level in the sole of the foot. In winter, while the total lipid distribution followed the same trend as that in summer, the absolute amounts slightly decreased, especially in the forehead and chest, as compared with those found in summer. Ceramide analysis showed that while a higher level was seen in the cubital fossa in summer, the level was highest in the forehead during winter. A seasonal comparison of ceramide mass revealed a slightly increased level in winter compared with summer, at almost all sites tested, except in the cubital fossa and dorsum pedis, reflecting seemingly enhanced keratinization in winter. These findings indicate that in young adults, the mass of ceramide remains steady at similar levels at various skin sites, providing maintenance of a pertinent water reservoir and the barrier function of the stratum corneum, even under different seasonal conditions.

Adult↗

Healing of chronic gastric ulcer depends on gastric mucosal prostaglandin synthesis.

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

6-Ketoprostaglandin F1 alpha↗

Reversed-phase high-performance liquid chromatographic analysis of hydroxyproline and proline from collagen by derivatization with dabsyl chloride.

A high-performance liquid chromatographic method for the analysis of hydroxyproline and proline has been developed. The method is based on the derivatization of the secondary amino group with dabsyl-chloride after blocking of the primary amino group with o-phthalaldehyde. Dabsyl-hydroxyproline and dabsyl-proline were separated from other amino acids by high-performance liquid chromatography in the gradient elution mode, and eluted at 10.27 and 16.02 min, respectively. The correlations between the peak areas of dabsyl-hydroxyproline and dabsyl-proline were linear in the range from 20-200 pmol, with equations y = 1.10x - 0.80 (r = 0.999) and y = 1.12x - 0.52 (r = 0.999), respectively. The method was applied to the analysis of rat tail collagen, and the contents of hydroxyproline and proline were 1.55 +/- 0.04 and 2.03 +/- 0.04 nmol/micrograms, respectively.

Animals↗

[Transcatheter hepatic segmental chemo-Lipiodol-embolization against hepatocellular carcinoma accompanied by tumor thrombosis in the portal vein].

We performed transcatheter hepatic segmental chemo-Lipiodol-embolization against hepatocellular carcinoma accompanied by tumor thrombosis in the portal vein. CT scan after embolization demonstrated good Lipiodol accumulation in the tumor thrombosis in some cases. In one resected case, remarkable necrosis of tumor thrombosis was proved histologically. In five non-resected cases, 6-month survival rate was 100%. We hope this therapeutic method can be useful for hepatocellular carcinoma with tumor thrombosis in the portal vein.

Aged↗

A case of acquired lymphangioma of the vulva.

A 46-year-old woman developed multiple papules on the right labium majus. A histological examination revealed acanthotic epidermis and dilated vessels in the papillary dermis. The clinical and histological features were compatible with those of lymphangiectasis or acquired lymphangioma of the vulva, which occurs after surgery or irradiation for cervical cancer. This patient, however, had no such past history. Acquired lymphangioma of the vulva arising without obvious causes seems to be unusual.

Endothelium↗

Quantitative analysis of stratum corneum lipids in xerosis and asteatotic eczema.

Sphingolipids, a major constituent of intercellular lipids, are an important determinant for both water-holding and permeability barrier function in the stratum corneum. To assess the pathogenic role of sphingolipids in the stratum corneum of dry skin disorders such as xerosis and asteatotic eczema in leg skin, ceramides were quantified by thin layer chromatography after n-hexane/ethanol extraction of resin-stripped stratum corneum and evaluated as micrograms/mg stratum corneum. In healthy leg skin (n = 49), there was age-related decline in the total ceramide, whereas xerosis (n = 25) and asteatotic eczema (n = 16) suffering significantly reduced water-holding properties, exhibited no definite decrease, rather slight increase in ceramide quantity with the same composition of each individual ceramide as compared to healthy age-matched controls. These data indicate that the seemingly elevated level of ceramide is an artificial effect due to inflammatory processes which result from susceptibility to dryness. Analysis of sebum-derived lipids present in the stratum corneum revealed that there was a significant decline in free fatty acids in xerosis and asteatotic eczema as compared to age-matched healthy controls, and a similar decline in triglycerides in the above three groups when compared to younger controls. Although the observed decrease in the stratum corneum lipids may well explain the high incidence of winter dry skin in older people, the progression toward asteatotic eczema can not be accompanied solely by a decrease in ceramide quantity, suggesting that the evolution of xerotic skin is associated with other moisturizing factors and/or environmental stimuli.

Adult↗

Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents.

The effects of sesamin, a potent inhibitor of delta 5-desaturase in polyunsaturated fatty acid biosynthesis, on the fatty acid compositions of tissue lipids and liver functions were examined in rodents. When a mixture of sesamin and episesamin (51.1:48.2, w/w) was given to rats at a dietary level of 0.5% for 13 days, the proportions of dihomo-gamma-linolenic acid significantly increased not only in the liver but also in plasma and hemocytes, suggesting an interference with delta 5-desaturation by these lignans. The sesamin preparation at the dietary level of 1% improved changes in various blood parameters of the mouse, such as aspartate aminotransferase and alanine aminotransferase activities, and the concentrations of total cholesterol, triglyceride and total bilirubin, caused by continuous inhalation of ethanol. In addition, sesamin showed a significant protective effect against the accumulation of fat droplets and vacuolar degeneration in the mouse liver, as confirmed on histological examination. Sesamin, at the level of 100 mg/kg body weight, also tended to prevent liver lipid accumulation by carbon tetrachloride in mice. These results indicate that sesamin and a related lignan compound have an ability to improve liver function.

Administration, Inhalation↗

[The influence of indoor environmental factors on the onset of allergic disease].

To predict and prevent the onset of allergic diseases, we studied the effects of indoor environmental factors, such as diet, on pregnant women and carried out follow-up studies on their infants. Blood samples were collected at random from women who were diagnosed as pregnant (n = 2045). Umbilical cord blood was collected at delivery (n = 1453). To evaluate the efficacy of food guidance, the pregnant women were divided into two groups--one receiving simple diet guidance starting in the later stages of pregnancy, and one receiving no guidance whatsoever. A follow-up survey on allergic symptoms was done on their two-year-old infants, revealing a lower incidence of symptomatic manifestations in the diet guidance group (p < 0.001). Respiratory symptoms (p < 0.05) were associated with maternal smoking and outside work during pregnancy. A study on food guidance in combination with environmental factors revealed that the incidence of respiratory symptoms in two-year-old infants whose mothers received diet guidance in a good indoor environment was held down to around 36.1%, while the incidence in infants whose mothers received diet guidance in a poor indoor environment was 48.1%.

Air Pollution, Indoor↗