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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 667 records · Page 37Linked to original sources

Molecular mechanism of adipogenic activation of the angiotensinogen gene.

Angiotensinogen gene expression is controlled in a tissue- and development-specific manner. Interestingly, the angiotensinogen gene is abundantly expressed in adipose tissues other than the liver, where it is mainly produced. We investigated the molecular mechanism of angiotensinogen gene expression in a 3T3-L1 preadipocyte-adipocyte system. Although angiotensinogen mRNA was barely detectable in preadipocytes, its levels increased significantly during differentiation. As a whole, the pattern of the change in transcriptional activity of the angiotensinogen promoter was similar to that of the angiotensinogen mRNA levels during adipogenic differentiation, indicating that the activation of the angiotensinogen promoter might be involved in the adipogenic differentiation-coupled gene expression. The proximal promoter region, from -96 to +22 of the transcriptional start site, was sufficient to confer adipogenic activation, and the proximal element from -96 to -52 of the transcriptional start site was necessary for this promoter stimulation. DNA-protein binding experiments showed that this proximal element specifically bound to a nuclear factor induced by adipogenic differentiation. These results suggest that the proximal promoter element from -96 to -52 plays a role in adipogenic activation of the angiotensinogen promoter.

3T3 Cells↗

Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency.

We identified a novel exonic mutation which causes exon skipping in the mitochondrial acetoacetyl-CoA thiolase (T2) gene from a girl with T2 deficiency (GK07). GK07 is a compound heterozygote; the maternal allele has a novel G to T transversion at position 1136 causing Gly379 to Val substitution (G379V) of the T2 precursor. In case of in vivo expression analysis, cells transfected with this mutant cDNA showed no evidence of restored T2 activity. The paternal allele was associated with exon 8 skipping at the cDNA level. At the gene level, a C to T transition causing Gln272 to termination codon (Q272STOP) was identified within exon 8, 13 bp from the 5' splice site of intron 8 in the paternal allele. The mRNA with Q272STOP could not be detected in GK07 fibroblasts, presumably because pre-mRNA with Q272STOP was unstable because of the premature termination. In vivo splicing experiments revealed that the exonic mutation caused partial skipping of exon 8. This substitution was thought to alter the secondary structure of T2 pre-mRNA around exon 8 and thus impede normal splicing. The role of exon sequences in the splicing mechanism is indicated by the exon skipping which occurred with an exonic mutation.

Acetyl-CoA C-Acetyltransferase↗

Mechanism of cAMP regulation of renin gene transcription by proximal promoter.

Renin is produced mainly by the kidney, and cAMP is a main positive regulator of its synthesis. This study was undertaken to analyze the molecular mechanism of cAMP-mediated regulation of Ren-1C gene transcription by the proximal promoter. We first showed that the promoter region from -365 to +16 of the mouse renin gene (Ren-1C) mediated the cAMP-induced chloramphenicol acetyltransferase gene expression in embryonic kidney-derived 293 cells. Deletion analysis and heterologous promoter assay disclosed that the proximal promoter region from -75 to +16 was able to activate chloramphenicol acetyltransferase expression by cAMP, and indicated that the proximal promoter element from -75 to -47 (RP-2 element) overlapping the TATA-like region was able to confer cAMP responsiveness. Electrophoretic mobility shift assay and DNase I footprinting analysis demonstrated that novel nuclear factors in 293 cells interacted with the RP-2 element, and that cAMP increased the binding activity of these nuclear factors to the RP-2 element. Furthermore, we demonstrated that cAMP enhanced the binding of nuclear factors derived from juxtaglomerular cells, the main production site of renin in the kidney, to the RP-2 element in vivo. These results suggest that the RP-2 element plays an important role in the cAMP-mediated regulation of Ren-1C gene transcription through the proximal promoter.

Base Sequence↗

Stomachic principles in ginger. III. An anti-ulcer principle, 6-gingesulfonic acid, and three monoacyldigalactosylglycerols, gingerglycolipids A, B, and C, from Zingiberis Rhizoma originating in Taiwan.

An anti-ulcer constituent, 6-gingesulfonic acid, and three monoacyldigalactosylglycerols, gingerglycolipids A, B, and C, were isolated from Zingiberis Rhizoma, the dried rhizome of Zingiber officinale Roscoe which was cultivated in Taiwan, together with (+)-angelicoidenol-2-O-beta-D-glucopyranoside. Based on chemical reactions and physicochemical evidence, the structures of 6-gingesulfonic acid, gingerglycolipids A, B, and C have been determined. In addition, the absolute stereostructure of (+)-angelicoidenol-2-O-beta-D-glucopyranoside was clarified on the basis of its synthesis from d-borneol. 6-Ginesulfonic acid showed weaker pungency and more potent anti-ulcer activity than 6-gingerol and 6-shogaol.

Animals↗

Crude drugs from aquatic plants. IV. On the constituents of alismatis rhizoma. (2). Stereostructures of bioactive sesquiterpenes, alismol, alismoxide, orientalols A, B, and C, from Chinese alismatis rhizoma.

Following the characterization of the triterpene constituents in Chinese Alismatis Rhizoma, we investigated the chemical structures of orientalols A, B, and C, isolated from the less polar fraction of the crude drug together with two known sesquiterpenes, alismol and alismoxide. On the basis of the chemical and physicochemical evidence, the structures of orientalols A, B, and C have been determined and those of alismol and alismoxide were revised. All five sesquiterpenes were found to show an inhibitory effect on the contraction of isolated bladder smooth muscle induced by carbachol.

Animals↗

Crude drugs from aquatic plants. V. On the constituents of alismatis rhizoma. (3). Stereostructures of water-soluble bioactive sesquiterpenes, sulfoorientalols a, b, c, and d, from Chinese alismatis rhizoma.

From the water-soluble portion of Chinese Alismatis Rhizoma, four bioactive sesquiterpenes, sulfoorientalols a, b, c, and d, were isolated and their structures having a sulfonic acid function were established on the basis of chemical and physicochemical evidence. In addition, two sulfoorientalol congeners were derived from alismol by sulfonation of the exo-methylene moiety. Sulfoorientalols and the synthetic congeners were found to inhibit the carbachol-induced contraction of isolated bladder smooth muscle of guinea pig.

Animals↗

[Crude drugs from aquatic plants. III. Quantitative analysis of triterpene constituents in alismatis rhizoma by means of high performance liquid chromatography on the chemical change of the constituents during alismatis rhizoma processing].

As a series of study on the evaluation of Alismatis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for ten triterpene constituents, alisols A, A monoacetate, B, B monoacetate, E 23-acetate, F, and G and 13,17-epoxyalisol A, 11-deoxyalisols B and B 23-acetate, has been developed. By the use of this HPLC method, the contents of these triterpenes in various Alismatis Rhizoma and the fresh rhizoma of Alisma oriental JUZEPC, originated from in China, Taiwan, and Japan were examined. Furthermore, the chemical change of the triterpene constituents during the drying process of the rhizoma of Alisma oriental has been investigated and it was found that the bioactive triterpenes of Alismatis Rhizoma such as alisol A and alisol A monoacetate were artificially formed during the drying process.

Chromatography, High Pressure Liquid↗

[The effect of doxorubicin on the unimpeded eruption rates of rat mandibular incisors].

We examined the effects of daily injections of doxorubicin, an anti-tumor drug, on unimpeded eruption rates, pulp cells, odontoblasts, periodontal ligament and dentine formation in the rat mandibular incisor. The experimental animals were intraperitoneally injected with 5 mg of doxorubicin/kg body weight/day for a period of 7 days. The eruption rates decreased gradually; and on the seventh day, the mean eruption rate had decreased to 14% of the control value. In addition, we noticed marked destruction of pulp cells and periodontal cells at the basal region of the incisor. The amount of dentine formation was measured using the tetracycline labeling method, but significant decreases in dentine formation were not observed. These results suggest that destruction of the basal tissues is related to inhibition of incisor eruption rates, but that tooth eruption is not related to dentine formation.

Animals↗

[A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type].

A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.

Aged↗

[Prospective study on the influence of social activity on development of dementia in the neurologically normal elderly].

We investigated the rate of development of dementia in 84 neurologically normal elderly subjects living in an old-age home (30 subjects, mean 77.2 years) or their own home 954, 73.7) prospectively. We examined cerebral blood flow (CBF), Hasegawa's scale (HS) and Kohs' block design test 6 to 9 years before this study (1991). HS and Kohs' IQ were significantly lower in the old-age home group than that in their own home group at that time. However, there were no demented subjects. Mortality was 21%, and we confirmed 9 dementia and 6 stroke cases during the period of observation. Twenty-seven percent of the old-age home group showed dementia in 1991. This rate was significantly higher than that for the elderly living in their own home (6.7%). Occurrence of stroke was also significantly higher in the former group than in the latter group. The subjects who developed stroke during observation showed a high incidence of dementia. Mean CBF measured on the first examination was significantly lower in dementia cases with stroke than in dementia cases without it. We performed MRI in 4 demented cases in 1991 (Fig. 1). Two cases showed no significant lesions and the other cases showed cerebral infarction which could cause dementia. These results indicate that life style and social environment may have significant effect on aging of the brain and on development of dementia in the elderly.

Aged↗

[The effect of age and disease on the MR imaging T2 low signal intensity area in the cerebral cortex].

We retrospectively studied magnetic resonance (MR) images of the brain in 139 patients (16 cases of Alzheimer's disease, 8 cases of Parkinson's disease, 53 cases of multiple cerebral infarct, 33 cases of other central nervous diseases, and 29 cases of peripheral neuropathy) between the age of 6 and 85 years old with a mean age of 60.6 +/- 18.5 to examine the appearance of T2 low signal intensity areas (T2CLIA) in the cerebral cortex. Motor, occipital, sensory or other cortices were evaluated with long repetition time/echo time (TR/TE) spin-echo sequences and staged into three grades in the motor cortex: none, partial, and whole; and two grades in the others: none or present. In general, T2CLIA was not seen in any cortex in patients less than 50 years old, then after 50 years old T2CLIA increased with age. Over 70 years of age T2CLIA appeared in 50.9% of patients in the whole motor cortex, 88.7% in either whole or partial motor cortex, 47.2% in the occipital cortex, and 20.8% in the sensory cortex. T2CLIA was not observed in other cortices. The incidence of T2CLIA appearance in the motor cortex was significantly higher in all central nervous diseases than in cases of peripheral neuropathy over 70. T2-CLIA showed a correlation with temporal lobe atrophy and white matter lesions in the motor cortex. In the sensory cortex, T2CLIA correlated with white matter lesions. These results suggest that T2-CLIA may correlate with age or accumulation of nonheme iron in the cortex associated with central nervous diseases.

Adolescent↗

[Flow cytometric analysis of prostatic adenocarcinomas after hormone therapy].

A DNA ploidy pattern of prostatic adenocarcinoma was studied by flow cytometry using the formalin-fixed, paraffin-embedded tissues obtained from 65 patients. These patients received hormone therapy preoperatively. Forty cases (61.5%) showed a diploid pattern, and 25 (38.5%) an aneuploid pattern. Comparing this ploidy pattern with histological classification, the aneuploid pattern was found in 13 cases (52%) of poorly differentiated group, 12 cases (48.0%) of moderately differentiated group and 0 case (0%) of well differentiated group. Thus, rate of aneuploid pattern increased with an increase in the grade of malignancy. Five years survival rate was 62.6% in the diploid group while it decreased to 30.9% in the aneuploid group. There was a significant difference between the two groups. In 23 cases with stage D, the ploidy pattern of primary region could be compared with that of metastatic region (lymph nodes). The prognosis of patients who exhibited the aneuploid pattern in metastatic region was significantly worse than that of other patients. These data suggested that flow cytometric DNA analysis of prostatic cancer materials after hormone therapy also produces meaningful information in predicting the prognosis of prostatic cancer.

Adenocarcinoma↗

[On a circular notice about herbs in Kisodani of mid-Edo period].

There is a circular notice about the gathering of herbs in Kiso-dani of Mid-Edo Period, and this notice is stocked at T. Simada's house in Nakatsugawa City. Thirty-two herb names and the prices are recorded in this notice, and some of them have the precise description of collection, medical parts, processing, general treatment, etc. Doeki Mimura contributed greatly to the development of Kiso Yakushu (crude drug), however, we cannot pass over the activity of Saiyaku-shi (medical officer) as well.

History, 18th Century↗

Non-N-methyl-D-aspartate receptor antagonism by 3-N-substituted 2,3-benzodiazepines: relationship to anticonvulsant activity.

Block of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) and kainate currents by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8- methylenedioxy-5H-2,3-benzodiazepine], a noncompetitive non-N-methyl-D-aspartate (AMPA/kainate) receptor antagonist, and two 3-N-substituted 3,4-reduced GYKI 52466 analogs was assessed in whole cell voltage-clamp recordings from cultured rat hippocampal neurons. In addition, the activity of the analogs was determined in the maximal electroshock seizure test and for protection against kainate-induced seizures in mice. The analogs of GYKI 52466 tested were the 3-N-methylcarbamyl [GYKI 53655; 1-(4-aminophenyl)-3-methylcarbamyl-4- methyl-3,4-dihydro-7,8-methylenedioxy-5H-2,3-benzodiazepine] and the 3-N-acetyl [GYKI 53405; 1-(4-aminophenyl)-3-acetyl-4-methyl-3,4-dihydro-7,8-methylenedioxy-5H-2, 3- benzodiazepine]. GYKI 53655 produced a concentration-dependent inhibition of AMPA- and kainate-induced currents with IC50 values of 1.1 and 1.5 microM, respectively; the corresponding values for GYKI 53405 were 3.8 and 5.0 microM. As blockers of AMPA currents, the analogs were 8- and 2.3-fold, respectively, more potent than the parent GYKI 52466. Kinetic analyses indicated increased association rates for the two 3-N-substituted analogs (2.5-2.6 x 10(5) M-1 sec-1) compared with GYKI 52466 (1.6 x 10(5) M-1 sec-1). The dissociation rates of GYKI 52466, GYKI 53405 and GYKI 53655 were inversely correlated with increasing blocking potency (2.9, 1.7 and 0.6 sec-1, respectively). Thus, the increased affinity of the 3-N-substituted analogs relates to their increased binding and decreased unbinding rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗