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Biomedical subjects

Y Shimura

Publications and source records attributed to Y Shimura.

At least 91 records · Page 5Linked to original sources
PubMed1990

The transmission of ambient noise and self-generated sound in the human body.

It is commonly understood that ambient noise and sounds produced by a pregnant woman herself are propagated into the body and reach the unborn child in the uterus. However, it would be unethical to study the propagation of sound to the fetus directly, so the present study, which aimed to clarify this process from an acoustical point of view, used the stomach as a model of the womb. The following points were demonstrated: For sound waves in the stomach, no interference such as occurs outside the body was observed. However, in the range 2 to 3 kHz, a resonance peak was visible, which was probably due to the gastric air space. Observing an average spectrum of songs showed that the sound pressure level (SPL(dB)) in the medium to lower range (below 3 kHz) tended to be higher in the stomach than outside.

Female↗
PubMed1990

Effects of pioglitazone on glucose and lipid metabolism in Wistar fatty rats.

Insulin resistance is one of pathogenic factors for non-insulin-dependent diabetes mellitus (NIDDM). Pioglitazone (5-[4-[2-(5-ethyl-2-pyridyl)-ethoxy]benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) is a promising candidate to lower hyperglycemia by reducing insulin resistance. The genetically obese-hyperglycemic rats. Wistar fatty, were used to test the action of pioglitazone, because they develop severe insulin resistance in the peripheral tissues (muscle and adipose tissue) and liver. Pioglitazone administered orally (0.3-3 mg/kg/d for 7 days) dose dependently reduced hyperglycemia, hyperlipidemia, and hyperinsulinemia in male fatty rats. Pioglitazone improved glucose tolerance and augmented the glycemic response to exogenous insulin and clearance of plasma triglyceride. These effects on glucose and lipid metabolism seem to be due to increased insulin sensitivity and responsiveness in the peripheral tissues, because pioglitazone increased insulin-stimulated glycogen synthesis and glycolysis in the isolated soleus muscles, and insulin-stimulated glucose oxidation and lipogenesis in adipocytes. The latter effects were not accompanied by any changes in insulin binding. The actions of insulin mimickers (vanadate and vitamin K5), which act on the post-insulin binding sites, on these metabolic events were also potentiated by pioglitazone. These findings suggest that pioglitazone can improve glucose and lipid metabolism by reducing insulin resistance on the post-binding system. Therefore, pioglitazone may be efficacious for treating human NIDDM.

Adipose Tissue↗
PubMed1990

Effects of pioglitazone on hepatic and peripheral insulin resistance in Wistar fatty rats.

Effects of pioglitazone (5-[4-[2-(5-etyl-2-pyridyl)ethoxy] benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) on peripheral and hepatic insulin resistance were examined using genetically obese-hyperglycemic rats, Wistar fatty. Pioglitazone was administered to fatty rats (3 mg/kg/d) and lean rats (10 mg/kg/d) for 6 days. Pioglitazone decreased hyperglycemia and hypertriglyceridemia without affecting hyperinsulinemia in the fatty rats, and significantly reduced plasma levels of triglyceride and insulin without altering normoglycemia in the lean rats. The same rats were subjected to an isotopic method combined with a euglycemic clamp technique for assessing insulin sensitivity in hepatic glucose production (HGP) and peripheral glucose utilization (PGU). HGP decreased and PGU increased in response to infused insulin in the lean rats but did not in the fatty rats, indicating that insulin resistance was present in the liver and peripheral tissues of the fatty rats. Treatment with pioglitazone restored the responses of HGP and PGU to infused insulin in the fatty rats, but did not produce any changes in the lean rats. When the same levels of glycemia and insulinemia were established by 480 mU/h of insulin in both treated and control fatty groups, PGU was 1.5-fold higher and HGP was 3-fold lower in the pioglitazone treated group. Pioglitazone also corrected the abnormality in hepatic enzyme regulation by insulin of the fatty rats: glucose-6-phosphatase decreased and glucokinase increased, suggesting the increased response of the liver to insulin and the resultant suppression of HGP. Therefore, pioglitazone is expected to be useful for treating abnormal glucose and lipid metabolism in non-insulin-dependent diabetes mellitus through reducing insulin resistance of the peripheral tissues and liver.

Animals↗
PubMed1990

Effects of pioglitazone on glucose and lipid metabolism in normal and insulin resistant animals.

The antidiabetic effects of pioglitazone (5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) were examined in normal, obese, and/or diabetic animals. When orally administered to genetically obese and diabetic yellow KK mice (2.4-24.5 mg/kg/d), and Zucker fatty rats (0.1-10 mg/kg/d) for 4 days, pioglitazone markedly decreased hyperglycemia, hyperlipidemia, hyperinsulinemia, and glucose intolerance characterized as insulin resistant states in these animals. Pioglitazone potentiated insulin-mediated glucose metabolism in the diaphragm and adipose tissues of yellow KK mice and enhanced the glycemic response to exogenous insulin in Zucker fatty rats. Four-day administration of pioglitazone (1 mg/kg/d) to aged and obese beagle dogs with moderate insulin resistance decreased plasma glucose and lipids in the fasting state, and postprandial rises in plasma triglyceride. Pioglitazone decreased plasma lipids but did not alter the plasma glucose level in young normal rats. Pioglitazone did not alter plasma glucose and lipid levels in streptozocin-diabetic rats. These results indicate that pioglitazone is effective on abnormal glucose and lipid metabolism associated with insulin resistance by enhancing insulin action on peripheral tissues. Therefore, pioglitazone is expected to be useful in treating obese non-insulin-dependent diabetes.

Adipose Tissue↗
PubMed1989

A secondary structure at the 3' splice site affects the in vitro splicing reaction of mouse immunoglobulin mu chain pre-mRNAs.

The expression of the IgM (immunoglobulin mu) heavy chain gene is known to be regulated at the post-transcriptional level. The two isoforms, the membrane-bound and secreted forms, are generated from the same gene by alternative processing at the 3' end of the primary transcript. The processing reactions involved are polyadenylation at the upstream poly(A) site (for the secreted form) and polyadenylation at the downstream poly(A) site coupled with splicing between exon C4 and exon M1 (for the membrane-bound form). The regulatory mechanism underlying these differential processing reactions is still not well understood. We investigated the splicing reaction between exon C4 and exon M1 in a HeLa nuclear extract using model transcripts containing the 5' and 3' splice sites of the C4-M1 intron. We found that the 3' splice site of the C4-M1 intron is sequestered in a stem-loop structure, which inhibits the splicing reaction in vitro. The inhibition by the stem-loop structure was also observed with a mouse lymphoma extract.

Animals↗
PubMed1989

Mutational analysis of pistil structure and development of Arabidopsis thaliana.

The developmental and morphogenetic process of pistil formation was examined by analysing flowers of wild type and six flower mutants of Arabidopsis thaliana, a small crucifer. The wild type is suggested to originate from two 'pistil-forming units' (carpels) arranged laterally against the axis of the inflorescence at a pistil primordium. Aberrant structures of the pistils of mutants indicate that a set of genes regulate each step of pistil development and morphogenesis, namely arrangement of the units at the pistil primordia, fusion of the units, growth of primordia, formation of the septum in the ovary, and formation of the stigma.

Brassica↗
PubMed1989

Effect of the cap structure on pre-mRNA splicing in Xenopus oocyte nuclei.

The effect of the 5' cap structure on the splicing of precursor mRNAs was investigated after the RNAs were injected into Xenopus oocyte nuclei. The precursor mRNAs synthesized in vitro in a prokaryotic transcription system with a dinucleotide, ApppG, as a primer, were extremely stable when injected into the nuclei yet behaved like uncapped pre-mRNAs in the in vitro splicing reaction. The ApppG-primed precursor mRNAs served as a control (uncapped) in the injection experiments, and their splicing reactions were compared with those of their capped (m7GpppG-primed) counterparts. The capped precursors were spliced more efficiently than the uncapped precursors. Examination of splicing of the precursor mRNA that contained three exons and two introns with a single molecule has revealed that the cap structure exerts its effect primarily on the 5'-proximal intron. Thus, the cap structure not only stabilizes precursor mRNAs but also plays a positive role in the splicing of precursor mRNAs in cells.

Animals↗
PubMed1989

Derangement in hepatic enzymes caused by sucrose-drinking and its implication for the development of hyperglycemia in female Wistar fatty rats.

Eight-week-old, female Wistar fatty rats and their lean littermates were given a 30% sucrose solution in addition to a laboratory chow diet and water for 7 weeks. The fatty rats were hyperinsulinemic and hyperlipidemic, but normoglycemic when they drank only water. The hepatic activities of insulin-inducible glucokinase (GK), pyruvate kinase (PK), and malic enzyme (ME) were higher in the fatty rats than in the lean rats, whereas the insulin-suppressible glucose-6-phosphatase (G6Pase) activity was similar in both types of rats, indicating the normal response of hepatic enzymes to hyperinsulinemia in the fatty rats. When they drank the sucrose solution, the fatty rats, but not the lean rats, developed hyperglycemia over 200 mg/dl. Plasma insulin and triglyceride concentrations increased in both types of rats. Although the hepatic activities of GK, PK, and ME in the lean rats, and PK and ME in the fatty rats increased in response to the increase in plasma insulin, GK activity decreased in the fatty rats. On the other hand, G6Pase activity increased in both types of rats. As a result, the G6Pase/GK ratio, which may reflect net glucose handling in the liver, increased twofold in the fatty rats, but did not alter in the lean rats. From these findings, we conclude that sucrose ingestion induces an increase in hepatic glucose production through derangement of the hepatic enzyme profile and that the resultant decrease in hepatic glucose handling may be one of the pathogenic factors participating in the development of hyperglycemia in Wistar fatty rats.

Animals↗
PubMed1989

Pathogenesis of hyperglycemia in genetically obese-hyperglycemic rats, Wistar fatty: presence of hepatic insulin resistance.

The present studies were designed to clarify the contribution of the liver to the development of hyperglycemia in Wistar fatty rats. The hepatic activities of insulin-inducible enzymes involved in glycolysis (glucokinase; GK and pyruvate kinase) and lipogenesis (glucose-6-phosphate dehydrogenase), were higher in fatty rats than in lean rats at 4 and 8 weeks of age because of the higher insulin levels in the former. Thereafter, the GK activities of fatty rats decreased slightly in spite of severe hyperinsulinemia, and did not differ from those of lean rats. In addition, fatty rats had higher levels of insulin-suppressible gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1, 6-diphosphatase. These findings indicate that the hepatic enzymes of fatty rats are resistant to insulin. This postulation was supported by the fact that the hepatic enzyme activities of fatty rats showed a lower response to changes in plasma insulin levels produced by fasting and refeeding. The G6Pase/GK ratio, which indicates net glucose handling in the liver, increased in fatty rats and decreased in lean rats with advancing age, suggesting that hepatic glucose production in fatty rats becomes dominant with advancing age. The changes in hepatic glycolytic intermediates supported this suggestion; the glycolytic steps both from glucose to glucose-6-phosphate and from phospho-enolpyruvate to pyruvate in fatty rats were accelerated at 5 weeks of age, but suppressed at 12 weeks of age. These results indicate that insulin resistance in the hepatic enzyme regulation may contribute to the development of hyperglycemia in Wistar fatty rats.

Aging↗
PubMed1988

Functional domains of the RNA component of ribonuclease P revealed by chemical probing of mutant RNAs.

The higher-order structure of the RNA component of ribonuclease P from Escherichia coli was analyzed using chemical probes. The secondary structure model which had been constructed from the comparative sequence analysis of the RNA was refined using the experimental data. In a mutant RNA (A89 RNA), which contains a G----A substitution at nucleotide 89, we detected a number of conformational alterations clustered between nucleotides 90 and 239. In view of the fact that A89 RNA is as catalytically active as wild-type RNA, but defective in association with the protein component, it is clear that the catalytic function of the RNA component resides on the structure which is not disrupted by the A89 mutation and that the structures altered by the mutation represent the region(s) interacting with the protein component. Another mutant (A329 RNA), which has a G----A substitution at nucleotide 329 and is defective in catalytic function, showed no detectable change in higher-order structure.

Endoribonucleases↗
PubMed1988

A rapid and efficient method for targeted random mutagenesis.

We describe a new rapid method for random introduction of single-nucleotide (nt) substitutions into a small segment of cloned DNA. A DNA fragment containing a sequence to be mutagenized is inserted into a multiple cloning site sequence of a vector plasmid. The plasmid is linearized with two adjacent cuts (generating 5' and 3' protruding ends) and then synchronously and unidirectionally digested with exonuclease III (Exo III) so that the 3' termini generated are localized within the target region. A non-complementary alpha-thiophosphate nucleotide is misincorporated into the 3' terminus generated by Exo III. Since the nucleotide analogue is resistant to the 3'-5' exonuclease activity of DNA polymerase I, its misincorporation into the 3' termini is irreversible. Then, the single-stranded region is filled-in with four canonical nucleotides, and the plasmid is recircularized. This procedure was used to mutagenize a specific region of the rnpB gene of E. coli. By sequencing 72 randomly selected clones, we found that 27 clones (37.5%) had nucleotide substitutions distributed within the desired region of a 55-nt-long segment of the gene. The procedure is simple and is applicable to any DNA molecule.

Base Sequence↗
PubMed1988

Requirement of ATP in the second step of the pre-mRNA splicing reaction.

The requirement of ATP in the second step of mRNA precursor splicing was examined by dissecting the two steps of the in vitro splicing reaction using a heat-treated nuclear extract from HeLa cells. When a mRNA precursor containing two exons and a single intron from the delta-crystallin gene was initially incubated for 60 min with the heated extract, thereby allowing only the first step of the splicing reaction to occur, and subsequently with a normal extract for 10 min, the final spliced product was produced without any lag. The production of the spliced molecule during the second incubation with the normal extract represents conversion of the intermediates already formed with the heated extract into the spliced product. The conversion was stimulated by the addition of ATP during the second incubation and inhibited by a nonhydrolyzable ATP analogue. These results led us to conclude that ATP is required for the second step of the splicing reaction.

Adenosine Triphosphate↗
PubMed1987

Preferential excision of the 5' proximal intron from mRNA precursors with two introns as mediated by the cap structure.

We have studied the effect of the 5' cap structure on the splicing of precursor mRNAs containing three exons and two introns within a single molecule in a HeLa nuclear extract. When a precursor mRNA was capped, the upstream intron was spliced out more efficiently than the downstream intron. The differential splicing reactions of the two introns are not due to differences in the intrinsic efficiency of splicing of each intron, since the preferential excision of the upstream intron was also observed when the positions of the two introns relative to the cap structure were reversed. When uncapped precursor mRNA was used as substrate, the downstream intron was spliced out appreciably, but splicing of the upstream intron was greatly reduced. Preincubation of the extract with cap analogues inhibited splicing of the upstream intron but not the downstream intron. Thus, the cap structure exerts its effect primarily on the 5' proximal intron.

HeLa Cells↗
PubMed1987

In vitro splicing of a chicken delta-crystallin pre-mRNA in a mammalian nuclear extract.

An in vitro splicing system was constructed using portions of chicken delta-crystallin pre-mRNA synthesized in vitro and a HeLa nuclear extract. Analysis of the reaction products revealed that about 25% of the pre-mRNA was precisely spliced at 30 degrees C in 2 h under the standard conditions. The other major products of the reaction detected were a 5'-exon fragment and three RNA species showing unusual electrophoretic mobilities on polyacrylamide gels. Structural analyses showed that these three RNAs contain a branch (lariat) structure as seen in the in vitro splicing reactions of human beta-globin, adenovirus, and yeast pre-mRNAs. In addition, methylation at the N-7 position of the blocking guanosine of the 5'-terminal cap structure of pre-mRNA has been suggested to play an important role in the splicing reaction.

Animals↗
PubMed1986

Mutations affecting two distinct functions of the RNA component of RNase P.

The effect of structural changes on the functions of the RNA component (M1 RNA) of ribonuclease P (RNase P) of Escherichia coli has been studied using the thermosensitive mutants of the rnpB gene. One of the mutants, ts709, has two G--A substitutions at positions 89 and 365 from the 5' end of M1 RNA. Of these substitutions, the one at position 89 from the 5' end is responsible for the phenotype of this mutant. Although the RNase P activity of ts709 is thermosensitive, the mutant M1 RNA has the same catalytic activity as the wild-type RNA. M1 RNA of another mutant, ts2418, has a G--A substitution at position 329. This mutant RNA has extremely low catalytic activity. The upstream mutational site of ts709 appears to play a role in the association with the protein subunit, whereas the mutational site of ts2418 is related to the catalytic function of M1 RNA.

Base Sequence↗
PubMed1986

L-aspartate ammonia-lyase and fumarate hydratase share extensive sequence homology.

Based on our recent determinations of the nucleotide sequences of the L-aspartate ammonia-lyase genes from Escherichia coli and Pseudomonas fluorescens, primary structures of the two L-aspartate ammonia-lyases and fumarate hydratases from Bacillus subtilis and E. coli (N-terminal partial sequence) were compared by computer analysis. These four enzymes exhibited a significant homology of at least 37%, implying that L-aspartate ammonia-lyase and fumarate hydratase share a common evolutionary origin. To authors' knowledge, this feature appears to be the first example showing that two kinds of enzymes catalyzing different types of reactions, albeit similar, share such a high degree of sequence homology.

Amino Acid Sequence↗