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H Morinaga

Publications and source records attributed to H Morinaga.

At least 19 recordsLinked to original sources
PubMed2006

Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat.

AIM: Spontaneously Diabetic Torii (SDT) rat is a new model of non-obese type 2 diabetes. SDT rats show severe ocular complications such as cataracts, tractional retinal detachment with fibrous proliferation and massive haemorrhaging in the anterior chamber. In the present study, blood glucose levels of SDT rats were controlled in order to examine whether these ocular complications are caused by hyperglycaemia. METHODS: SDT rats were treated with an insulin implant to control blood glucose. To evaluate retinal function, we used electroretinograms (ERG) and measured vascular endothelial growth factor (VEGF) concentrations within the aqueous humour. Finally, we studied retinal flat-mounts and trypsin digestion to evaluate vascular abnormalities in SDT rats. RESULTS: Forty-four-week-old SDT rats displayed an increase in VEGF concentrations within the aqueous humour and significant prolongation of the peak latencies in ERG (Sigma(OP(1)-OP(4)); Sprague-Dawley (SD): 146.2 +/- 1.06 ms; SDT: 166.3 +/- 2.38 ms; SDT + insulin: 149.2 +/- 1.83 ms). Retinal flat-mounts of SDT rats showed venous dilation and meandering vascular networks. Furthermore, acellular capillaries were observed in the retinal trypsin digestion. Insulin treatment prevented these ocular abnormalities in SDT rats. CONCLUSIONS: These findings indicate that ocular complications of SDT rats are caused by hyperglycaemia. The features of SDT rats indicate their usefulness for the future study of diabetic retinopathy.

Animals↗
PubMed2003

Stimulation of bacterial activity by the addition of different PACs.

The effect of bacterial adhesion on powdered activated carbon on bacterial activity in non-toxic wastewater was studied and the difference of powdered activated carbon species on the stimulation of bacterial activity was also evaluated using eight kinds of powdered activated carbon. Pure cultures of Escherichia coli K-12, which can reduce NO3- to NO2- in anoxic conditions, were used. Specific nitrate reduction activity was used as an indicator of bacterial activity. The higher specific nitrate reduction rates were noted in cultures with powdered activated carbon than without powdered activated carbon or with Kaolin. The specific nitrate reduction rate with powdered activated carbon was up to about 1.4 times as highas those without powdered activated carbon. The stimulation of bacterial activity was induced by the adhesion of bacterial cells onto powdered activated carbon. There are powderedactivated carbons that can stimulate bacterial activity, whereas not all the powdered activated carbon can stimulate bacterial activity. Surface characteristics like Brunauer-Emmett-Teller specific surface areas, total surface acidity, oxygen functional groups, total surface basicity, surface charge, pH(pzc), iodine number, concentrations of metals, electric resistance, free radical concentration and adsorption capacity of formate did not related with the stimulation of the bacterial activity.

Carbon↗
PubMed2001

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

Androstenedione↗
PubMed2001

Genomic organization and neuronal cell type specific promoter activity of beta isoform of Ca(2+)/calmodulin dependent protein kinase II of rat brain.

The gene encoding the beta isoform of rat Ca(2+)/calmodulin-dependent protein kinase II was cloned, and its exon-intron organization was analyzed. The gene consisted of 21 exons spanning more than 80 kilobase pairs and the coding sequence was made up of 20 exons. Each discrete functional unit, such as the ATP-binding site, the autophosphorylation site responsible for Ca(2+)-independent activity, the calmodulin binding site, and the link structure, was encoded by a single exon. All splice junction sequences flanking the introns conformed to the consensus splice junction sequence and the GT-AG splice rule. The site of transcription initiation was -78 bases from the initiation codon as determined by 5' RACE analysis. The promoter activity of the gene was analyzed using neuroblastomas, as well as non-neuronal cell lines. Neuronal cell type-specific promoter activity was found in the 5'-upstream region -66 to -35 bp from the transcription initiation site. Silence elements were found further upstream at -222 to -123 bp and -576 to -323 bp. A protein bound to the -66 to -35 region was found in the nuclear extract of rat brain, including the cerebellum, forebrain, and brainstem, by gel mobility shift assay.

3T3 Cells↗
PubMed2001

The subnuclear three-dimensional image analysis of androgen receptor fused to green fluorescence protein.

To establish the novel approach in order to distinguish the transcriptionally active androgen receptor (AR) from the transcriptionally inactive AR, we performed the three-dimensional construction of confocal microscopic images of intranuclear AR. This method clearly distinguished the subnuclear localization of transcriptionally active AR tagged with green fluorescent protein (AR-GFP) from the transcriptionally inactive AR-GFP. Transcriptionally active AR-GFP mainly produced 250-400 fluorescence foci in the boundary region between euchromatin and heterochromatin. Although the AR-GFP bound to such antiandrogens as hydroxyflutamide or bicalutamide translocated to the nucleus, they homogeneously spread throughout the nucleus without producing any fluorescence foci. Antiandrogenic environmental disrupting chemicals, such as 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, vinclozolin, or nitrofen, also disrupted the intranuclear fluorescence foci. A point mutation (T877A) resulted in the loss of ligand specificity in AR-GFP. Even in this mutant receptor, agonists, such as dihydrotestosterone, hydroxyflutamide, or progesterone, produced the fluorescence foci in the nucleus, whereas the transcriptionally inactive mutant binding bicalutamide was observed to be spread homogeneously in the nucleus. Taken together, our findings suggest that, after nuclear translocation, AR is possibly located in the specific region in the nucleus while demonstrating clustering tightly depending on the agonist-induced transactivation competence.

Active Transport, Cell Nucleus↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 26). Detection of 1,3-dinitrobenzene-induced histopathological changes in testes and epididymides of rats with 2-week daily repeated dosing.

As part of a collaborative work, male rats were administered 1,3-dinitrobenzene (1,3-DNB) daily at 0, 25 and 50 mg/kg/day from the age of 6 weeks for 4 weeks (4-week exp.), or at 25, 50 and 75 mg/kg/day from the age of 8 weeks for 2 weeks (2-week exp.). After the end of each administration period, all survivors were sacrificed, and their testes and epididymides were removed, weighed and examined histopathologically. The following results were obtained. In the 4-week exp.: At 50 mg/kg/day, the weights of testes and epididymides showed decrease with macroscopic atrophy. The testicular spermatogenic epithelium showed decrease in the number of sperm-spermatocytes, degeneration/necrosis, giant cell formation and vacuolation, reduction in sperm counts also being evident in the ducts of the epididymides. In the 2-week exp.: At 50 and 75 mg/kg/day, the weights of testes and/or epididymides showed decrease with macroscopic atrophy. Several histopathological changes in the testes and epididymides were essentially the same changes as in the group given 50 mg/kg/day in the 4-week exp., with a clear relation. These results indicate that a 2-week administration period is sufficient to detect testicular and epididymal histopathological changes induced by 1,3-dinitrobenzene in male rats.

Administration, Oral↗
PubMed1999

Isolation of deoxycytidine kinase from Ehrlich carcinoma cells by affinity chromatography based on a substrate analog, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine++ +.

Deoxycytidine kinase from Ehrlich carcinoma cells was purified 10400-fold by ammonium sulfate fractionation and affinity chromatography using Sepharose 4B coupled to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine , with a yield of 45%. The purified enzyme preparation showed a single major band with a molecular weight of 32000 on SDS-PAGE. The enzyme phosphorylated deoxyadenosine, deoxyguanosine, cytidine, and several deoxycytidine analogues as well as deoxycytidine. Also, the kinetic parameters of the enzyme for the substrates were estimated.

Animals↗
PubMed1998

Implications of heat shock/stress proteins for medicine and disease.

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

Animals↗
PubMed1996

Gene of rat Ca2+/calmodulin-dependent protein kinase II alpha isoform -- its cloning and whole structure.

The gene encoding the alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II was cloned, and its exon-intron organization was analyzed. The coding region of cDNA consists of 18 exons spanning more than 50 kilobase pairs. Each of the discrete functional units, such as the ATP-binding site, the autophosphorylation site responsible for Ca2+-independent activity, the calmodulin-binding site, and link structure is encoded by a single exon. The largest and smallest exons consist of 229 and 41 base pairs, respectively. All splice junction sequences flanking the introns conform to the consensus splice junction sequence and the GT-AG splice rule.

Adenosine Triphosphate↗
PubMed1996

[Antigenicity tests of a new antineoplastic agent S-1].

The antigenicity was tested of a new antineoplastic agent S-1 (a combination of tegafur (FT), CDHP and potassium oxonate (Oxo)) in mice and guinea pigs. 1. Male BALB/c or C3H/He mice were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and human serum albumin (HSA). S-1 was administered by oral gavage, and the other compounds were administered intraperitoneally with adjuvant (alum). In the heterologous passive cutaneous anaphylaxis (PCA) test, using Sprague-Dawley rats as recipients, no IgE antibodies against S-1, CDHP, or Oxo were detected to any serum obtained from the sensitized mice, and no eliciting antigenicities were seen for CDHP or Oxo. 2. Male Hartley guinea pigs were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and HSA. S-1 was administered by oral gavage, and the other compounds were administered subcutaneously with Freund's complete adjuvant (FCA). The homologous PCA test, active systemic anaphylaxis test, and passive hemagglutination test showed no production of antibodies against S-1, CDHP, or Oxo in any sensitized guinea pig, and no eliciting antigenicities for CDHP or Oxo. 3. Female Hartley guinea pigs were sensitized with S-1 subcutaneously with FCA. The active cutaneous anaphylaxis test revealed that S-1 did not induce cell-mediated delayed type hypersensitivity. 4. These results indicated that S-1, Oxo, and CDHP were not antigenic in mice and guinea pigs.

Administration, Oral↗
PubMed1996

[Immunotoxic effects of a new antineoplastic agent S-1 in mice--comparison with S-1, UFT and 5-FU].

The immunotoxicity of S-1, which is a new antineoplastic agent, was investigated in BALB/c mice. S-1 contains tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molecular ratio of 1:0.4:1. 5-fluorouracil (5-FU) and UFT were used as reference drugs. S-1 and reference drugs were administered by oral gavage for 7 days. The high dose employed in this study was determined as the maximally tolerated dose of a 9-day repeated-dose study in sarcoma 180-bearing mice. Decreased body weight was observed in mice treated with 5-FU and UFT but not in those treated with S-1. A significant decrease in thymus and spleen weight was observed in S-1-, UFT- and 5-FU-treated mice, and the degree was same for the three drugs. Though the number of white blood cells decreased dose-dependently for the three drugs, S-1 had the weakest effect. The number of red blood cells also decreased, but the effect was not dose-dependent, and its magnitude was the same for the 3 drugs. S-1 induced a dose-dependent decrease in the IgM antibody PFC response to sheep erythrocytes. The delayed type hypersensitivity response used a footpad reaction method was significantly suppressed at the highest dose of S-1. 5-FU and UFT suppressed humoral and cell-mediated immunity in almost the same manner as S-1. The degree of suppressive effects was greater on the humoral immune response than on the cell-mediated immune response. The number of CFU-GM colonies was significantly decreased in the highest dose group of each drug and in a lower group as well in S-1-treated mice. This finding might reflect the fact that S-1 induced continuous high levels of 5-FU in the blood. Under these experimental conditions, S-1 induced immunosuppressive effects in BALB/c mice, and the degree of suppression was almost same as that induced by 5-FU and UFT.

Animals↗
PubMed1995

Neutron spectrum and yield of the Hiroshima A-bomb deduced from radionuclide measurements at one location.

In this paper measurements of the radionuclides of 36Cl, 41Ca, 60Co, 152Eu and 154Eu in samples from Hiroshima, which were exposed to neutrons of the A-bomb explosion, are interpreted. In order to calculate the neutron spectrum at the sample site, neutron transport calculations using Monte Carlo techniques were carried out. Activation profiles in a granite mock-up irradiated with reactor neutrons could be reproduced by this method using DS86 input parameters. The calculated neutron spectrum at the sample site for non-thermal neutrons is identical to that obtained in DS86, but contains some 50% more thermal neutrons. The influence of parameters like soil composition, source terms and air humidity on the activation of these radioisotopes is discussed. The granite-covered earth at the sample site, for example, hardens the spectrum in comparison with DS86 values. Even when using a fission spectrum pointing downward and neglecting air humidity one cannot explain our 36Cl measurements. If the effective thermal neutron fluences, that have a similar ratio of resonance integral to thermal neutron capture cross sections obtained from 36Cl, 41Ca and 152Eu, are averaged, a bomb yield of about 16 kt is deduced in agreement with a bomb yield of (15 +/- 3) kt estimated in DS86.

Calcium Radioisotopes↗
PubMed1994

An in vivo study of hepatic and splenic interleukin-1 beta mRNA expression following oral PSK or LEM administration.

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL-1 beta production by liver macrophages, and the produced IL-1 beta activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.

Administration, Oral↗
PubMed1992

[Single dose toxicity studies of suplatast tosilate (IPD-1151T)].

Single dose toxicity studies of suplatast tosilate (IPD-1151T) were carried out in mice, rats and dogs of both sexes. The results were as follows: 1. The LD50 values of IPD-1151T were as follows: Mice, 12,500 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Mice 81 (male) and 96 (female) mg/kg in intravenous route; Rats, 10,000 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Rats, 96 (male) and 93 (female) mg/kg in intravenous route; Dogs, 2,124 (male) and 2,660 (female) mg/kg in oral route. On the LD50 values, no sexual difference was apparent in all species, but the species difference was noted between the rodent and dog. LD50 values of dog were lower level than those of rodent. 2. As toxic signs, mucous diarrhea with specific smell was noted in orally administered rodent. In addition, rats showed soiled fur in the perianal. In intravenous route, the rodent showed dyspnea, tonic convulsion and lateral position and deaths occurred within 10 min in mice and within 30 min in rats after administration. Dog showed toxic signs similar to those in rodents and deaths occurred within 3 hours. 3. In pathological examinations, dead mice and dogs administered orally showed lung congestion, liver fading or slight hemorrhage in the endo-and/or exocardium. Dead rodent administered intravenously showed only slight hemorrhage and congestion in the lung. Alive mice, rats and dogs showed no remarkable changes. 4. The main cause of deaths seemed to be respiratory disturbance in all species.

Animals↗
PubMed1990

Accelerator mass spectrometry of 36Cl produced by neutrons from the Hiroshima bomb.

Accelerator mass spectrometry was performed at the Munich tandem laboratory to determine 36Cl/Cl ratios of samples from a tombstone exposed to neutrons from the Hiroshima bomb. The ratios were determined from the surface to deeper positions. The depth profile of 36Cl/Cl can be used for estimating the neutron energy distribution and intensity near the hypocentre in Hiroshima.

Chlorine↗
PubMed1989

Carcinoma arising in fibroadenoma of the breast--a case report and review of the literature.

A 47 year old woman with two isolated lumps in her right breast underwent an excisional biopsy and the histological findings of both lesions revealed fibroadenoma with an in situ lobular carcinoma. Patey's modified radical mastectomy was performed after which careful follow-up was continued. To date, a total 161 cases of carcinoma arising in a fibroadenoma have been reported in the world literature and a review of these literature is given following the case report.

Adenofibroma↗
PubMed1989

[Acute toxicity studies of propiverine hydrochloride].

Acute toxicity studies of propiverine hydrochloride (P-4) were carried out in mice, rats and dogs of both sexes. 1. The LD50 values of P-4 were as follows: Mice; 410 (male) and 323 (female) mg/kg in oral route, 223 (male) and 283 (female) mg/kg in subcutaneous route and 36 (male and female) mg/kg in intravenous route, Rats; 1000 (male) and 1092 (female) mg/kg in oral route, 1632 (male) and 1411 (female) mg/kg in subcutaneous route, and 22 (male) and 25 (female) mg/kg in intravenous route. On the LD50 values, no sexual difference was apparent but the species difference between mice and rats observed to be present in oral and subcutaneous routes. The approximate lethal doses of P-4 in dogs were 987-1137 mg/kg for male and 865-894 mg/kg for female in oral route, and the values were almost same as those in rats of oral route. 2. Major toxic signs such as clonic convulsion, bradypnoea, dyspnoea, decreased spontaneous activity and hematuria were observed in mice and rats. Furthermore mydriasis in rats, and transitory salivation and/or vocalization in mice and rats were observed. In some rats, sedation, salivation, soil at hypogastrium, rale and emaciation were detected from the next day of oral administration. In dogs, toxic signs such as vomiting, tremor, tonic and/or clonic convulsion, mydriasis and gasping were observed. 3. Pathological changes observed in dead animals were congestion of lungs, liver and kidneys in all routes, congestion and hemorrhage in digestive tracts in oral route, inflammatory changes at the injection site in subcutaneous route. In addition, retention of hematuria in urinary bladder in rats of oral and subcutaneous routes, the hemorrhagic changes of heart, atonia of urinary bladder and retention of urine in dogs were observed. 4. The main cause of death seemed to be respiratory disturbance in all species and the weakness in a few rats of oral route.

Animals↗