PubMed HealthSearch

Biomedical subjects

H Nishino

Publications and source records attributed to H Nishino.

At least 19 recordsLinked to original sources

Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis.

Squalene inhibited the effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), such as increased 32Pi incorporation into phospholipids of HeLa cell membrane, induction of Epstein-Barr-virus early antigen in Raji cell and induction of ornithine decarboxylase in mouse skin. Squalene also markedly suppressed the promoting activity of TPA on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.

Animals

Potent preventive action of alpha-carotene against carcinogenesis: spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by alpha-carotene than by beta-carotene.

Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

4-Nitroquinoline-1-oxide

Inhibitory effects of dihydroagarofuran sesquiterpenes on Epstein-Barr virus activation.

To search for possible antitumor promoters, we carried out a primary screening of thirty-seven dihydroagarofuran sesquiterpenes from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, using their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of these sesquiterpenes, triptofordin F-2 (Takaishi et al., 1988), 1,2,6,8,15-pentaacetoxy-9-benzoyloxy-4-hydroxy-beta-dihydroagarofuran and triptogelin A-1 (Takaishi et al., 1990) were observed to significantly inhibit the EBV-EA activation at low doses. Based on the results, the structural requirements for the activity of these compounds were discussed [corrected].

Anticarcinogenic Agents

Potent anti-tumorigenic effect of tubeimoside 1 isolated from the bulb of Bolbostemma paniculatum (Maxim) Franquet.

Tubeimoside 1, one of the new triterpenoid saponins from the bulb of Bolbostemma paniculatum (Maxim) Franquet, had an anti-inflammatory effect on mouse ear edema induced by arachidonic acid and 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, a potent anti-tumorigenic effect of tubeimoside 1 was observed in 2-stage carcinogenesis of mouse skin after oral administration as well as topical application. Thus, tubeimoside 1 appears to be a promising agent for cancer chemoprevention.

Administration, Topical

Yucca leaf protein (YLP) stops the protein synthesis in HSV-infected cells and inhibits virus replication.

Yucca leaf protein (YLP), an inhibitor of tobacco mosaic virus isolated from the leaves of Yucca recurvifolia Salisb., exhibited potent activity against herpes simplex virus type 1 (HSV-1) with no cytotoxicity below 300 micrograms/ml. The inhibitory dose was varied with the time of addition; 50% effective concentrations (ED50) of YLP were 3, 19 and 95 micrograms/ml when YLP exposure was begun 3 h before virus infection, 0 h and 3 h after infection, respectively. This protein also inhibited the multiplication of herpes simplex virus type 2 and human cytomegalovirus. YLP has been shown to have a weak virucidal activity at higher concentrations. Analysis of early events following infection showed that YLP affected viral penetration in HeLa cells but did not interfere with adsorption to the cells. YLP was found to exert strong inhibition of protein synthesis in virus-infected cells but not in uninfected cells. This selective effect can be considered to attribute mainly to the antiviral activity of YLP.

Animals

Sialyl cholesterol enhances the development of grafted neurons and motor recovery.

Trophic actions of alpha-sialyl cholesterol (SC) and its sialidase-tolerant derivative, alpha-(3 beta-hydroxysialyl) cholesterol (SCt), were carried out on the development of midbrain neurons both in vitro and in vivo transplantation studies. Low to moderate concentrations of SC (0.01 to 0.05 micrograms/ml) facilitated neurite extension but had no effects on cell survival of primary cultured midbrain neurons. However, high concentration of SC (0.1 micrograms/ml) disturbed both neurite genesis and cell survival. SCt had a similar effect on midbrain neurons. At higher concentrations, SC and SCt induced concentration-dependent morphological changes in astrocytes from flat to fibrous. The effect on astrocytes was stronger in SCt than SC. At highest concentration tested (20 micrograms/ml), the proliferation of astrocytes was completely blocked, cells became detached and finally died. This effect of SC and SCt was partially blocked by simultaneous application of aFGF. Following dopaminergic cell grafting in vivo, SC and SCt had biphasic effects: a low dose (0.2 mg/kg, SC) enhanced motor recovery at 4 and 6 weeks after transplantation, while the highest dose (20 mg/kg, SC) disturbed motor recovery at all periods tested. These effects on motor recovery were paralleled by an effect on neurite genesis as studied by tyrosine hydroxylase immunostaining. Thus, at low concentrations, SC and SCt are neurotrophic agents that stimulate the development and differentiation of dopaminergic neurons.

Animals

Anti-tumor-promoting activities of afromosin and soyasaponin I isolated from Wistaria brachybotrys.

Afromosin [1] and soyasaponin I [2] isolated from Wistaria brachybotrys exhibited remarkable inhibitory effects on mouse skin tumor promotion, and afromosin also exhibited a significant inhibitory effect on pulmonary tumor promotion. The combined effects of these compounds on the two-stage skin carcinogenesis were also examined, and it was concluded that the combination of 1 with 2 enhanced the inhibitory effect.

9,10-Dimethyl-1,2-benzanthracene

Anti-neoplastic effect of halocynthiaxanthin, a metabolite of fucoxanthin.

We have reported that fucoxanthin, a natural carotenoid, inhibited the growth of human neuroblastoma GOTO cells. In the present study, we show that a metabolite of fucoxanthin, halocynthiaxanthin, which is isolated from sea squirt Halocynthia roretzi, has a more potent inhibitory effect. Halocynthiaxanthin (5 micrograms/ml) caused complete suppression of GOTO cell proliferation, whereas fucoxanthin reduced the growth rate by only 88.8% compared with the control, at day 2 after the drug treatment. Furthermore, halocynthiaxanthin also inhibited the growth of other human malignant tumor cells. Thus halocynthiaxanthin seems to be a promising anti-neoplastic agent.

Antineoplastic Agents

Responses of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons to chemical stimuli in behaving rhesus monkeys.

1. Extracellular single neuron activity was recorded in the lateral hypothalamic area (LHA) of awake, behaving monkeys, with particular regard to the feeding-related functional characteristics of glucose-sensitive (GS) versus glucose-insensitive (GIS) neurons. Firing rate changes were recorded by means of carbon fiber, multibarreled glass microelectrodes during 1) microelectrophoretic application of various chemicals, 2) gustatory and olfactory stimulation, and 3) a high fixed-ratio schedule (FR) bar press feeding task. 2. In 336 neurons examined, 91 (27%) were suppressed by electrophoretically administered glucose, and so they were designated as GS cells. The 245 neurons (73%) in which the firing rates did not change during glucose applications were pronounced GIS. The 179 GS and GIS cells tested exhibited different responses to the catecholamines (CAs), noradrenaline (NA) and dopamine (DA), both of which are intimately involved in the control of feeding. More GS neurons responded to NA than did GIS cells; the predominant effect of both CAs on GS neurons was inhibition. 3. The taste responsiveness of 111 LHA neurons was examined. Fifty-seven cells (52%) showed responses to gustatory stimulation. Of 50 GS neurons tested, 33 (66%) exhibited firing rate changes to tastes. On the contrary, only 24 (39%) of the 61 GIS neurons examined responded to gustatory stimuli. Activity changes of GS neurons commonly occurred to two or more tastants, in distinction to the relative gustatory specificity shown by GIS cells. 4. Two hundred fifty-six (84%) of the 303 neurons tested responded during one or more phases of the bar press feeding task. Most activity changes occurred during the bar press (BP) and reward (RW) periods, however numerous phasic responses to cue light (CL) and cue tone (CT) were also observed. A higher proportion of the GS neurons showed task-related activity changes than did the GIS cells (77, 95% and 179, 81%, respectively). GS neurons responded more during the BP phase and to the food reward; GIS cells were more responsive during the CL that enabled acquisition and the CT that signaled reward. Thus GS neurons were responsive during the acquisition and consumption of reward, whereas GIS cells responded to external cues signaling both of these events. The gustatory neurons displayed specific task-related activity changes only in the CL (GIS cells) and BP phases (GS neurons), that is, in phases most intimately involved in sensory-motor integration. 5. Two-thirds of the 30 GS neurons tested were responsive to both gustatory and olfactory stimulation as opposed to only one-third of GIS cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Palm carotene inhibits tumor-promoting activity of bile acids and intestinal carcinogenesis.

The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly.

9,10-Dimethyl-1,2-benzanthracene

Lymphoscintigraphy of head-and-neck cancer.

To achieve the visualization of regional lymph nodes by lymphoscintigraphy, 21 patients with head-and-neck cancer were studied with the aid of 99mTc-labeled rhenium sulfur colloid (99mTc Re). Four injection sites were selected; the injections were given into the subcutaneous tissue of the parietal area of 11 patients, into the submucosa of the retromolar area of 6 patients, into the subcutaneous tissue of the postauricular area of 2 patients, and into the thyroid glands of 2 patients. Lymphoscintigraphy was done three hours after the injection. The cervical regions were visible in 85.7% of the patients on the affected side and in 90.5% on the healthy side. The visualization comprised the following regions: submental, submandibular, deep cervical, accessory, and supraclavicular regions. In total, 102 nodes were visualized on the affected side (average 4.8 per patient) and 110 nodes in the healthy side (average 5.5). Histologically, 15 of 21 patients had lymph nodes metastases and 6 did not. Of these 21 patients, 66.7% (14/21) had confirmed lymph node metastases in the visualized regions. This technique appears to be a relatively easy and efficient method of imaging the regional lymph nodes in head-and-neck cancer both before treatment and after neck surgery.

Aged

Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives.

Novel N-[[dialkylamino)ethoxy]benzyl]benzamide derivatives (II-1-51), derived from the structural modification of metoclopramide (I), were synthesized and examined for their pharmacological activities. Among them, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (II-34) which exhibited well balanced gastrointestinal prokinetic and antiemetic activities was selected as a new type of gastrointestinal prokinetic agent.

Amines

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.

Animals

Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumor-promoting activities.

To search for possible anti-tumor-promoters, fourteen flavones obtained from the root of Scutellaria baicalensis were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Among these flavones, 5,7,2'-trihydroxy- and 5,7,2',3'-tetrahydroxyflavone showed remarkable inhibitory effects on the EBV-EA activation, and the effect of the latter on Raji cell cycle was also examined by flow cytometer. These two flavones exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals

Overshoot and high equilibrium in body temperature responses of rats to ambient heat: relation to thermoregulatory ability and improvement in estimation of survival time in a hot environment.

Physiological significance of body temperature responses to ambient heat (BTRAH) with high overshoot or a high equilibrium phase was studied in relation to thermoregulatory ability. Subsequently, an attempt was made to predict survival time (ST) by measuring the period required to attain a colonic temperature (Tco) of 42.0 degrees C (t42.0), whereas ST hitherto having been calculated on the basis of a period until Tco attains 42.5 degrees C (t42.5). Tco of rat was monitored continuously with a Cu-Co thermocouple during exposure to an ambient temperature (Ta) of 42.5 degrees C. The lower the overshoot temperature (Tos) or the equilibrium temperature (Teq), the longer the rats survived in a hot environment. The present findings further suggest that these two types of BTRAH are immature variations of the typical triphasic BTRAH which is characteristic of heat resistant individuals. A new regression line of ST (Y) as a function of the t42.0 (X) was obtained for most rats as follows: Y = 0.963X + 43.85 (male); and Y = 0.973X + 39.10 (female). This equation enabled to calculate ST without thermal death. However, the former approach based on t42.5 must be applied yet in small number of rats which showed the irregular BTRAHs with Tos or Teq higher than 42.0 degrees C. Delayed influence on survival and fecundity at a Ta of 24 degrees C were not found during one year following this hyperthermia up to 42.5 degrees C.

Animals

[Survey of the antibody to HCV in National Leprosarium Suruga].

Blood specimens from 210 leprosy patients (average age 67.4 years old) and 84 staff members (average age 43.5 years old) in National Leprosarium Suruga were tested for anti-HCV antibody using Ortho's Ab ELISA system. Among the patients, 17 patients had chronic hepatic dysfunction as well as leprosy. Twenty of the 210 patients (9.5%) had anti-HCV antibody in their blood. Eleven of the 17 patients (65%) with chronic hepatic dysfunction were positive for anti-HCV antibody. Only one of the staff member was anti-HCV antibody positive. This high positive ratio of anti-HCV antibody in the leprosy patients is similar to the results of another research reported from National Leprosarium Oku Komyo-En. We, therefore, conclude that the prevalence of anti-HCV antibody in leprosy patients is higher than that of the general population and that anti-HCV antibody is related closely to chronic hepatic dysfunction. Some investigators have recently reported that there was an increased incidence of hepatocellular carcinoma in leprosy patients. And so, it is speculated that this is due to the high prevalence of the hepatitis C virus. However, the reason for this high prevalence of anti-HCV antibody in the sample is obscure.

Adult

Inhibitory effects of (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone on proliferation of human malignant tumor cells.

A butenolide compound (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone (KNK-41), was shown to have strong anti-tumor activity. KNK-41 inhibited the proliferation of various kinds of human malignant tumor cells, such as HeLa (cervical carcinoma), HGC-27 (gastric cancer), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow cytometric analysis indicated that KNK-41 caused an arrest in G0/G1 phase of the cell cycle. However, it scarcely affected DNA synthesis and the level of c-myc mRNA. These results suggest that the growth-inhibitory effect of KNK-41 is the result of G0/G1 arrest and not of the suppression of DNA synthesis and/or c-myc expression.

4-Butyrolactone

Delta 12-prostaglandin J2 mimics heat shock in inducing cell cycle arrest at G1 phase.

Using a human neuroblastoma cell line GOTO, the effects of delta 12-prostaglandin (PG) J2 on the modulation of cell cycle progression and protein synthesis were examined in comparison with those caused by heat shock (HS). delta 12-PGJ2 induced G1 arrest, the peak of which was obtained at 24 h and continued for 72 h. HS was found to induce G1 arrest earlier than delta 12-PGJ2. Furthermore, sequential HS could maintain G1 arrest. delta 12-PGJ2 induced the synthesis of several heat shock proteins (HSPs) in a manner similar to HS. Using immunoblot analysis, HSP72 was detected prior to inducing G1 arrest and accumulated during the subsequent 72h. The content of HSP72 induced by HS also correlated well with the induction, release, and maintenance of G1 arrest. In addition, both delta 12-PGJ2 and HS induced HSP72 mRNA and simultaneously suppressed N-myc mRNA expression. These results suggest that delta 12-PGJ2 and HS regulate cell cycle progression of GOTO cells via similar mechanisms.

Blotting, Northern