Biomedical subjects

T Yoshihara

Publications and source records attributed to T Yoshihara.

At least 91 records · Page 5Linked to original sources

PubMed1997

Independence of feeding-associated circadian rhythm from light conditions and meal intervals in SCN lesioned rats.

Free-running period of the feeding-associated circadian rhythm was assessed in suprachiasmatic nucleus (SCN) lesioned rats under three different conditions using a feeding-fasting (FF) paradigm; restricted feeding (RF) with meal intervals of 24 h (T = 24 h) under 24 h light-dark cycle (LD), RF with T = 24 h under continuous dim light (dim LL), and RF with T = 25 h under dim LL. After the termination of RF, the rats were subjected to FF regimen five times repeatedly, in which food and water were available for 7 days, followed by total food deprivation for 3 days with free-access to water. Free-running period, which was measured with reference to the prefeeding activity peak during food deprivation, was very close to 24 h and was not different under three conditions. It is concluded that the feeding-associated circadian rhythm has a major period close to 24 h, which is not affected either by light conditions nor by meal intervals.

Animals↗

PubMed1997

An unusual case of laryngeal carcinoma metastasizing to the small intestine.

An unusual case of laryngeal carcinoma metastasizing to the small intestine is reported. The patient was admitted to our hospital due to hoarseness, sore throat and dyspnoea. Pathological examination on the laryngeal mass revealed it to be moderately differentiated squamous cell carcinoma, staged as T4N0M0. A total laryngectomy and right modified neck dissection were performed. Over two years after the operation a small intestinal tumour was found, with a resultant resection of the ileum and sigmoid colon. An infiltration of the cell nests of squamous cell carcinoma were present at the submucosal regions of the ileum. These findings indicated that the laryngeal cancer had already metastasized to the small intestine at the time of the initial treatment.

Aged↗

PubMed1997

Cell transformation mediated by homodimeric E2A-HLF transcription factors.

The E2A-HLF fusion gene, created by the t(17;19)(q22;p13) chromosomal translocation in pro-B lymphocytes, encodes an oncogenic protein in which the E2A trans-activation domain is linked to the DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF), a member of the proline- and acidic amino acid-rich (PAR) subfamily of bZIP transcription factors. This fusion product binds to its DNA recognition site not only as a homodimer but also as a heterodimer with HLF and two other members of the PAR bZIP subfamily, thyrotroph embryonic factor (TEF) and albumin promoter D-box binding protein (DBP). Thus, E2A-HLF could transform cells by direct regulation of downstream target genes, acting through homodimeric or heterodimeric complexes, or by sequestering normal PAR proteins into nonfunctional heterocomplexes (dominant-negative interference). To distinguish among these models, we constructed mutant E2A-HLF proteins in which the leucine zipper domain of HLF was extended by one helical turn or altered in critical charged amino acids, enabling the chimera to bind to DNA as a homodimer but not as a heterodimer with HLF or other PAR proteins. When introduced into NIH 3T3 cells in a zinc-inducible vector, each of these mutants induced anchorage-independent growth as efficiently as unaltered E2A-HLF, indicating that the chimeric oncoprotein can transform cells in its homodimeric form. Transformation also depended on an intact E2A activator region, providing further support for a gain-of-function contribution to oncogenesis rather than one based on a dominant-interfering or dominant-negative mechanism. Thus, the tumorigenic effects of E2A-HLF and its mutant forms in NIH 3T3 cells favor a straightforward model in which E2A-HLF homodimers bind directly to promoter/enhancer elements of downstream target genes and alter their patterns of expression in early B-cell progenitors.

3T3 Cells↗

PubMed1997

Effect of transportation on the composition of bronchoalveolar lavage fluid obtained from horses.

OBJECTIVE: To study the effects of extended transportation on the composition of bronchoalveolar lavage fluid (BALF) obtained from horses. ANIMALS: 30 horses (14 males, 16 females: 25 Thoroughbreds and 5 Thoroughbred-Arabian cross-breds; 27 to 30 months old) without a history or clinical signs of respiratory tract disease. Bronchoalveolar lavage was performed on nontransported control horses (groups 1 and 2) and transported horses (group 3). PROCEDURE: 20 horses were used to determine the effect of 41 hours of transportation on the composition of BALF (group 3). Bronchoalveolar lavage fluid was analyzed for recovered volume, number and distribution of nucleated cells, total protein and phospholipid concentrations, and phospholipid composition. RESULTS: Total number of nucleated cells in BALF from group-3 horses increased by approximately four-fold after transportation. Total protein concentration in BALF from group-3 horses also increased by approximately fivefold after transportation. Total phosphorus concentrations in group-3 horses decreased significantly from time 0 to immediately after transportation. In group-3 horses, the most characteristic change in composition of BALF after transport was a significant decrease in the concentration of phosphatidylglycerol. CONCLUSION AND CLINICAL RELEVANCE: The decrease in phosphatidylglycerol concentration in BALF after transportation indicates a reduction in the quantity of surfactant. This change may reflect either a decreased production of surfactant by alveolar type II epithelial cells or an increased removal of surfactant from the alveolar region. It is likely that extended transportation resulted in a decreased concentration of surfactant in BALF. Such a decrease may reduce the pulmonary defence mechanisms in the alveolar region, possibly resulting in infection.

Aging↗

PubMed1997

[An old female case of vero-cytotoxin-producing Escherichia coli O-157: H7 infection].

It is well known that verocytotoxin-producing Escherichia coli O-157 : H7 infection can be severe in elderly persons. We report an 82-year-old female case of verocytotoxin-producing Escherichia coli O-157 : H7 infection. She was admitted to our hospital because of bloody diarrhea. The hemolytic-uremic syndrome (HUS) was not occurred, but systemic edema, ascites, pleural effusion and pulmonary edema with hypoxyemia gradually appeared. Treatment with human immunoglobulin in addition to fluid therapy, antibiotics, diuretics and human serum albumin resulted in dramatic improvement. Management of complications such as sepsis and electrolyte disturbance caused by this infection was considered to be important in elderly patients.

Aged↗

PubMed1997

Effect of gentamycin on the melanosomes in the stria vascularis of the pigmented guinea pig: an ultrastructural study.

Melanosomes of the stria vascularis in gentamycin (GM)-intoxicated guinea pigs were examined ultrastructurally. Experimental animals were given GM sulfate intramuscularly in a daily adjusted dose of 100 mg/kg for 15 consecutive days (group A), and 150 mg/kg for 5 consecutive days (group B). Melanosomes of the intermediate cells in group B significantly increased in number in comparison with those in group A and the control group. Melanosomes in the apical turn outnumbered those in the basal turn in all three groups. Cytochemically, Na+, K(+)-ATPase activity was also demonstrated in the marginal cells. There was little difference in the degree of enzyme activity between groups A, B and the control group. The role and significance of melanosomes of the stria vascularis are discussed.

Animals↗

PubMed1997

Kinetic analysis of furosine and pentosidine in CAPD patients.

Advanced glycation end products (AGEs) have been noted in the peritoneal tissue of continuous ambulatory peritoneal dialysis (CAPD) patients, and this may cause an increase in membrane permeability. In vivo and in vitro kinetic analysis was carried out on furosine and pentosidine, early and late glycation products. Plasma furosine and pentosidine were measured by HPLC in patients with renal dysfunction with or without diabetes mellitus (DM) and dialysate pentosidine and furosine in CAPD patients. Only those dialysis patients without residual renal function were used in this study. Plasma furosine was remarkably high in DM, hemodialysis (HD), and CAPD patients. Plasma pentosidine appeared to depend on renal function and was not influenced by diabetic condition. Plasma pentosidine was significantly higher in CAPD than HD patients. A weak positive correlation was noted between dialysate and plasma furosine and pentosidine, indicating the main source of furosine and pentosidine in PD effluent to be plasma. Serial dialysate sampling showed furosine and pentosidine to increase linearly. Mean dialysate/plasma (D/P) of furosine and pentosidine were 0.043 and 0.012, respectively. Protein-bound product size and in situ formation of furosine in the peritoneal cavity would be the reason for these differences in D/P. In situ formation of early glycation products in the peritoneal cavity may be concluded to take place in CAPD patients, and high plasma pentosidine may lead to its accumulation in tissue, resulting, possibly, in pathological change.

Adult↗

PubMed1996

Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.

The E2A-HLF (for hepatic leukaemia factor) fusion gene, formed by action of the t(17;19) (q22;p13) chromosomal translocation, drives the leukaemic transformation of early B-cell precursors, but the mechanism of this activity remains unknown. Here we report that human leukaemia cells carrying the translocation t(17;19) rapidly died by apoptosis when programmed to express a dominant-negative suppressor of the fusion protein E2A-HLF, indicating that the chimaeric oncoprotein probably affects cell survival rather than cell growth. Moreover, when introduced into murine pro-B lymphocytes, the oncogenic E2A-HLF fusion protein reversed both interleukin-3-dependent and p53-mediated apoptosis. The close homology of the basic region/leucine zipper (bZIP) DNA-binding and dimerization domain of HLF to that of the CES-2 cell-death specification protein of Caenorhabditis elegans suggests a model of leukaemogenesis in which E2A-HLF blocks an early step within an evolutionarily conserved cell-death pathway.

Amino Acid Sequence↗

PubMed1996

A 45-bp proximal region containing AACA and GCN4 motif is sufficient to confer endosperm-specific expression of the rice storage protein glutelin gene, GluA-3.

A 45-bp proximal region of the rice glutelin promoter (-104/-60) containing two putative cis-elements, the AACA motif and GCN4 motifs, was fused to a truncated CaMV 35S promoter (-90/+9; -90 delta 35S)/GUS. The 45-bp fragment specifically enhanced the promoter activity in endosperm tissue of transformed tobacco. A substitution mutation of the GCN4 motif reduced the promoter activity, whereas mutation of the AACA motif increased the activity in the embryo as well as in the endosperm. These results suggest that the GCN4 motif generally enhances the promoter activity but that the combination of the two motifs confers the endosperm specificity. Furthermore, the function of the two motifs was dependent on the orientation and/or distance from a G-box element in -90 delta 35S, suggesting that synergistic interaction between the factors that recognize those motifs and the G-box element is important for transcriptional regulation.

Base Sequence↗

PubMed1996

Methamphetamine stimulates the release of neuropeptide Y and noradrenaline from the paraventricular nucleus in rats.

Effects of methamphetamine (MAP) on the extracellular neuropeptide Y (NPY) and noradrenaline (NA) levels were examined in the vicinity of the paraventricular nucleus (PVN) of freely moving rats by means of push-pull perfusion. The NA and NPY levels increased significantly in 30-60 min and reached the maximum level in 90-120 min after intraperitoneal administration of MAP. The effects were dose-dependent. The maximum levels were 1.6-fold of the pretreatment level for NPY and 7-fold for NA, respectively, when 5.0 mg/kg b.w. of methamphetamine was administered. It is concluded that MAP stimulates the releases of paraventricular NPY and NA, but the effect is more strong for NA than for NPY.

Animals↗

PubMed1996

Characterization of common cis-regulatory elements responsible for the endosperm-specific expression of members of the rice glutelin multigene family.

Glutelin is the most abundant storage protein in rice, which is expressed specifically in the endosperm of maturing seed. Glutelin is encoded by about 10 genes per haploid genome, which are clearly divided into two subfamilies (GluA and GluB). Most of them are coordinately expressed during seed maturation in spite of the remarkable divergence in the 5'-flanking regions between members of two subfamilies. In order to identify the common regulatory mechanisms responsible for the endosperm-specific expression, various cis-regulatory elements in the 5'-flanking region of the glutelin GluB-1 gene were characterized by studying the expression of chimeric genes that consisted of the sequentially deleted or mutagenized promoter and a beta-glucuronidase (GUS) reporter gene in transgenic tobacco seeds. The essential cis-regulatory elements governing the spatially and temporally specific expression of the glutelin gene expression were located within the first 245 bp of the promoter region of the GluB-1 gene from the site of initiation of transcription. The AACA motif between positions -73 and -61 common to all the six genes for glutelin sequenced to date and is repeated between positions -212 and -200 is implicated in the seed-specific expression. The GCN4 motif between positions -165 and -158 and between positions -96 and -92 that is conserved at homologous sites in all the members of glutelin gene family is also involved in the seed-specific regulation. However, both are required for the high level of seed-specific expression, because deletion of the region containing one set of both elements or substitution mutation of the AACA or GCN4 motif substantially reduced the activity. As a whole, our results suggest the combinatorial interaction of the elements in regulation of the glutelin gene expression.

Base Sequence↗

PubMed1996

Small increase in triplet repeat length of cerebellum from patients with myotonic dystrophy.

Myotonic dystrophy (DM) is genetically characterized by abnormal expansion of an unstable CTG trinucleotide repeat, located in the 3'-untranslated region of mRNA encoding the family of serine-threonine protein kinases. DNA extracted from various organs of patients with DM was analyzed by the Southern blotting method. We identified differently expanded bands in DNAs from various tissues from patients with DM. In studying the length of the CTG repeat in different regions of the brain, we found a noticeably small increase in repeat length in the cerebellum compared with other tissues. While this phenomenon has been reported in other triplet repeat diseases such as Huntington disease, spinocerebellar ataxia type 1, and dentatorubral-pallidoluysian atrophy, we are the first to describe it in DM. Although the mechanism of expansion of the triplet repeat remains to be defined, the tissue-dependent somatic mosaicism suggests that its occurrence may depend on the differentiated state of each tissue.

Cerebellum↗

PubMed1996

High concentrations of immunoreactive inhibin in the plasma of mares and fetal gonads during the second half of pregnancy.

Plasma concentrations of immunoreactive (ir)-inhibin were measured in seven pregnant mares from around Day 140 of gestation to Day 2 after parturition using a heterologous bovine-based radioimmunoassay (RIA). Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, progesterone and relaxin were also measured in the same samples. A marked increase in plasma concentrations of ir-inhibin, FSH and LH occurred between Day 220 and Day 300 of gestation but the concentrations of all three hormones returned to baseline by about Day 320 (three weeks before parturition). In contrast, circulating concentrations of the three placental hormones, oestradiol-17 beta, progesterone and relaxin, increased during the final weeks of pregnancy and then decreased markedly to basal values within two days of parturition. There was a positive correlation between circulating concentrations of ir-inhibin and FSH (r = 0.75, P < 0.01) rather than the expected negative correlation. ir-inhibin was not detected in homogenates obtained at Day 190 of pregnancy and form term placenta, but high concentrations of ir-inhibin were present in homogenates of fetal and newborn gonads. Despite the high concentrations of ir-inhibin in these homogenates, they failed to exert any suppressive bioactivity on FSH secretion by rat pituitary cells cultured in vitro. Furthermore, immunohistochemical staining revealed the presence of inhibin in the interstitial cells of equine fetal gonads at Day 190 of gestation. These findings demonstrate for the first time that high concentrations of ir-inhibin, LH and FSH are secreted into the peripheral circulation of the mare during the second half of pregnancy. However, ir-inhibin present in the plasma of pregnant mares appears to be biologically inactive. This hormone is not presumed to be of placental origin but it is proposed that either the enlarged fetal gonads or the maternal ovaries, or both of these organs, may be a source of inhibin in response to the coincident increase in circulating concentrations of LH and FSH.

Animals↗

PubMed1996

cis-regulatory elements responsible for quantitative regulation of the rice seed storage protein glutelin GluA-3 gene.

The 897 bp 5' flanking region of the rice storage protein glutelin gene (GluA-3) was analyzed to define cis-regulatory elements responsible for the seed specific expression by progressive 5' deletions and gain-of-function experiments using a truncated CaMV 35S promoter (-90/+9). These constructs were transcriptionally fused either to the firefly luciferase (LUX) or beta-glucuronidase (GUS) reporter gene and introduced into tobacco. It was shown that a 121 bp sequence between -437 and -317 from the transcriptional start site is important for the quantitative regulation of the GluA-3 gene expression. This region contained at least two functionally different cis-regulatory elements. One acts as a general positive element and the other is involved in a specific negative regulation in non-seed tissues.

Animals↗

PubMed1996

Effects of restricted daily feeding on neuropeptide Y release in the rat paraventricular nucleus.

Extracellular neuropeptide Y (NPY) in the vicinity of the paraventricular nucleus (PVN) and the NPY concentrations in the PVN, arcuate nucleus of the hypothalamus (ARC), and the nucleus tractus solitarius (NTS) were measured in rats under ad libitum and restricted daily feeding (RF) where meal was supplied at a fixed time of day. The extracellular NPY levels did not vary significantly between 0600 and 2200 in rats under ad libitum feeding but were increased before meal and decreased immediately after mean supply under the RF regimen. Similarly, the NPY concentrations in the PVN, ARC, and NTS were increased immediately before meal. When meal was omitted at the regular mealtime, the extracellular NPY levels were not decreased rapidly, and the NPY concentration in the PVN remained at a low level. Rats were subjected to the feeding-fasting paradigm after the termination of RF. The extracellular NPY levels were returned to basal levels during the feeding period but were elevated during the fasting period at almost the same time as that for meal supply under the RF regimen. It is concluded that the prefeeding enhancement of the NPY release in the PVN under the RF regimen is regulated by the feeding-associated circadian rhythm.

Animals↗

PubMed1996

Prefeeding release of paraventricular neuropeptide Y is mediated by ascending noradrenergic neurons in rats.

The neuronal system responsible for the release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) was examined in rats under food deprivation and restricted daily feeding (RF). The ascending noradrenergic bundle (NAB) of neurons from the brain stem were destructed by microinjection of 6-hydroxydopamine (6-OHDA), and the extracellular NPY level in the PVN was measured by push-pull perfusion. 6-OHDA significantly reduced the extracellular norepinephrine level in the PVN to 15% of the control value when injected into the PVN and to 40% when injected into the midbrain ventral NAB. 6-OHDA administration into the NAB affected neither the deprivation-induced increase nor the feeding-induced decrease in the extracellular NPY. The amount of food intake after refeeding was not changed by the 6-OHDA treatment. On the other hand, 6-OHDA injection into the PVN or NAB not only decreased the extracellular NPY level, the amount of food intake was not change by the 6-OHDA treatment. It is concluded that the NAB is involved in the prefeeding NPY release in rats under RF but not in the deprivation-induced NPY release.

Animals↗

PubMed1996

Dissociation of paraventricular NPY release and plasma corticosterone levels in rats under food deprivation.

Extracellular neuropeptide Y (NPY) in the vicinity of the paraventricular nucleus (PVN) as well as NPY concentrations in the PVN were measured in rats under ad libitum feeding and 2-day and 10-day food deprivation. Plasma corticosterone levels were not changed by 2-day food deprivation but were increased by subsequent refeeding. In contrast, the extracellular NPY levels were increased by 2-day food deprivation and were decreased rapidly by refeeding. The NPY concentrations were also increased and increased further by refeeding. On the other hand, plasma corticosterone levels were elevated by 10-day food deprivation and were decreased by subsequent refeeding. The extracellular NPY levels were also increased by food deprivation and decreased gradually after refeeding. However, the postprandial levels were still elevated when plasma corticosterone levels were returned to the basal levels. The NPY concentrations were also increased and increased further by refeeding. The amount of food intake after refeeding was positively correlated with the extracellular NPY levels. It is concluded that extracellular NPY levels in the PVN do not necessarily covariate with plasma corticosterone levels in rats under food deprivation.

Animals↗

PubMed1995

Ultrastructure and three-dimensional imaging of epimyoepithelial islands in benign lymphoepithelial lesions.

Benign lymphoepithelial lesions of the salivary glands associated with Sjögren's syndrome are characterized by extensive infiltration of lymphoid cells, atrophy of acini and the presence of so-called epimyoepithelial islands. This report describes ultrastructural and three-dimensional reconstructive studies of epimyoepithelial islands performed at Tokyo Women's Medical College. Ultrastructural examination showed that these islands are composed mainly of epithelial cells containing intermediate filaments and/or tonofilament bundles, scattered lymphocytes and plasma cells. Myoepithelium-like cells containing myofilaments were sometimes found in the peripheral portion of the myoepithelial islands. Also, mitotic figures were rarely found in these islands. Three-dimensional reconstructive study revealed that the epimyoepithelial islands are not isolated cell clusters but are continuous hypertrophic duct-like structures. These results suggest that the epimyoepithelial islands are derived from proliferating duct epithelial cells, especially those of large peripheral ducts.

Actin Cytoskeleton↗