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Biomedical subjects

M Horiuchi

Publications and source records attributed to M Horiuchi.

At least 163 records · Page 9Linked to original sources
PubMed1996

Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency.

A quantitative study of the effect of carnitine deficiency on expression of glycolytic and gluconeogenic enzymes was performed using juvenile visceral steatosis mice which are systemically deficient in carnitine. The amounts of glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared to heterozygotes and normal controls at 2 and 8 weeks. Liver-type phosphofructokinase, however, did not differ significantly. The abundance of fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not at 8 weeks. A part of these changes could not be explained by the plasma glucose or insulin level. Carnitine administration restored the mRNA of these enzymes to normal levels. These results suggest that carnitine deficiency affects the expression of these liver enzymes.

Age Factors↗
PubMed1996

Differentiation of vaccine virus from field isolates of feline panleukopenia virus by polymerase chain reaction and restriction fragment length polymorphism analysis.

In an attempt to distinguish feline panleukopenia virus (FPLV) live vaccine strains from FPLV field isolates in Japan, we compared restriction fragment length polymorphisms (RFLP) of polymerase chain reaction (PCR)-amplified fragments of live FPLV vaccine strains with those of FPLV Japanese field isolates. On the basis of nucleotide sequence differences between PLI-IV, a live vaccine strain, and FPV-483, a recent field isolate, two restriction enzymes, Dra I and Afa I, were selected for PCR-RFLP analysis of nucleotide (nt) differences at nt 3695 and 4508, respectively. Three live vaccine strains including the PLI-IV strain could be distinguished from the Japanese field isolates by their PCR-RFLP patterns by Afa I, but one live vaccine strain was indistinguishable from the Japanese isolates when Dra I and Afa I were used. The Japanese field isolates were divided into two groups by the profile of PCR-RFLP patterns generated by Dra I and Afa I, suggesting that PCR-RFLP analysis using several enzymes provides a good genetic estimate of strain differentiation. No isolate that shows a Dra I-negative/Afa I-negative pattern has emerged in Japan, indicating the possibility that the live vaccine viruses with a Dra I-negative/Afa I-negative pattern, such as the PLI-Iv strain, are candidates for use as live FPLV vaccine strain in Japan where they can be genetically distinguished from field strains.

Animals↗
PubMed1996

Immunological and virological study of sudden deafness.

Thirty-three patients with sudden deafness and 11 controls were selected from the patients admitted to the Department of Otolaryngology, Tokai University Hospital from November 1990 to October 1991. Viral titers were measured for mumps, adenovirus, rubella, measles, herpes simplex virus (HSV), varicella zoster virus (VZV), rhinosyncytial virus, cytomegalo-virus (CMV), and mycoplasma pneumoniae in 33 sudden deafness patients and 11 controls at a 2-week interval. In 20 of 33 sudden deafness patients and 5 of 11 controls, autoantibodies of rheumatoid factor (RF), anti-mitochondrial antibody (AMA), anti-nuclear antibody (ANA), anti-parietal cell antibody (APA), anti-smooth muscle antibody (ASA), and anti-type II collagen antibody were studied. Viral titer study did not reveal any significant change either in the patients or in the controls, whereas autoantibody study revealed a relatively high incidence for ASA in the patients as compared with the controls. The relatively high incidence for ASA suggests that immune-mediated processes may be involved in the etiology of sudden deafness.

Adenoviridae↗
PubMed1996

Isolation of canine parvovirus from a cat manifesting clinical signs of feline panleukopenia.

Twenty-seven feline parvovirus (FPV) isolates were recovered from cats clinically diagnosed with feline panleukopenia (FPL) for assessing antigenic and genomic properties of FPL viruses (FPLV) recently prevalent among cats in Japan. All isolates, with the exception of one novel isolate, FPV-314, possessed homologous properties, and their subgroups in FPVs were identified as FPLV. The FPV-314 isolate, which was from a 1.5-year-old cat which manifested clinical signs of FPL and died on the 13th day after the first medical examination, was finally identified as canine parvovirus (CPV) because it lacked a specific antigenic epitope commonly detected in FPLV and mink enteritis virus and because the nucleotide sequence of the capsid protein gene was almost identical to those of CPV-2a and -2b antigenic type strains recently prevalent among dogs in Japan. The present result together with our previous findings (M. Mochizuki, R. Harasawa, and H. Nakatani. Vet. Microbiol. 38:1-10, 1993) indicates the possibility that CPV and FPLV undergo mutual interspecies transmission between dogs and cats, and it is postulated that they may cause disease in some adventitious hosts.

Animals↗
PubMed1996

In vivo gene transfer and gene modulation in hypertension research.

Transgenic technologies and homologous recombination approaches have been useful for studying the roles of specific genes in systemic hypertension. Recently, we and others have introduced the use of in vivo gene transfer to study the effects of local gene overexpression or inactivation in hypertension. Using in vivo gene transfer for the blood vessel, we have documented the direct hypertrophic action of local angiotensin and the growth-inhibitory effect of nitric oxide. In vivo gene transfer is also an effective method for discovering the unknown functions of a newly cloned gene. Using this approach, we identified the in vivo growth-inhibitory action of the angiotensin II type 2 receptor. In addition, we have developed a novel strategy using transcriptional factor "decoy" oligonucleotides to regulate the interaction of cis- and trans-acting factors involved in the modulation of gene expression in vivo. Thus, the decoy approach can "switch" on or off specific genes in selective tissues in vivo, thereby influencing local gene expression and tissue function. For example, using decoy oligonucleotides, we have "turned on" renin gene expression in the rat liver, in which it is usually not expressed, resulting in increased hepatic and plasma renin levels. Thus, in vivo gene transfer technology provides us with a new tool for in vivo characterization of genes involved in hypertension that has potential application in human therapy.

Animals↗
PubMed1996

Vasoactive substances regulate vascular smooth muscle cell apoptosis. Countervailing influences of nitric oxide and angiotensin II.

This study tests the hypothesis that the control of vascular smooth muscle cell (VSMC) apoptosis is regulated by the antagonistic balance between vasoactive substances such as NO and angiotensin II (Ang II). Moreover, it is postulated that the cellular signaling pathways involved in regulating vessel tone are also coupled to the regulation of programmed cell death. Using an in vitro model system, we documented that the addition of NO donor molecules S-nitroso-N-acetylpenicillamine or sodium nitroprusside to VSMC dose-dependently induced apoptosis as documented by DNA laddering and quantified by analysis of cellular chromatin morphology. The mediator role of the guanylate cyclase signaling pathway in NO-induced apoptosis was evidenced by (1) induction of apoptosis by the 8-bromo-cGMP analogue, (2) potentiation of NO-induced apoptosis by cGMP-specific phosphodiesterase inhibition, and (3) the prevention of NO-induced apoptosis by the inhibition of the cGMP-dependent protein kinase 1 alpha. In contrast, Ang II directly antagonized NO donor- and cGMP analogue-induced apoptosis via activation of the type I Ang II receptor. These findings suggest that the countervailing balance between NO and Ang II may determine the overall cell population within the vessel wall by regulating genetic programs determining cell death as well as cell growth.

Angiotensin II↗
PubMed1996

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Sar1, Ile5]Ang II, most (> 90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), Bmax for the AT2 receptor was significantly decreased (62 +/- 17 and 25 +/- 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 Bmax (54 +/- 12 fmol/mg protein, n = 4). AT2 Bmax or Kd values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant. AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

Adult↗
PubMed1996

Potential transforming-ability by internal deletion of the bovine c-myb gene.

Two kinds of bovine c-Myb, the 75 kDa full-length (FL) c-Myb from the thymic type of sporadic bovine lymphosarcoma (SBL) cells, and 65 kDa deleted (DEL) c-Myb, which is an internally deleted form (85 amino acids corresponding to the negative regulatory domain) from calf-type SBL were found. To investigate the relationship between internal deletion and transforming capacity, we constructed retroviral vectors carrying cDNA that encoded either FL- or DEL-Myb protein, and transfected them to mouse fetal liver cells. In spite of the high trans-activating capacity of DELMyb, DELMyb and FLMyb showed no significant difference in oncogenic capability by measurement of colony formation in soft agar or in methylcellulose medium. Thus, the internal deletion of the c-myb gene is competent for transactivation but not directly relevant to transformation of mouse hemopoietic cells.

3T3 Cells↗
PubMed1996

[Prognostic factors in squamous cell carcinoma of the head and neck].

The clinical and histological factors predicting survival of patients with head and neck cancer were discussed. Recent reports with multivariate analysis focusing on clinical prognostic factors revealed that staging of nodal metastases is most significant. Number and size of metastatic nodes can be evaluated as factors to predict the outcome of advanced cancer. The number of positive nodes over 4 may be associated with poor prognosis. A scoring system of histological grading has been developed at this primary site. The mode of invasion or depth of invasion of cancer may predict the metastases to regional nodes. The research on molecular pathology is ongoing in head and neck cancer. No independent prognostic factor is yet available in clinical practice.

Carcinoma, Squamous Cell↗
PubMed1996

[Clinico-pathological predictive indicators in squamous cell carcinoma of the head and neck].

The significance of prognostic factors that may predict the clinical outcome of patients with head and neck cancer was discussed. Many indicators can be grouped into three categories, patient factors, tumor factors and treatment factors. The most significant indicator of prognosis seems to be pathological nodal stage. Factors such as clinical stage, resectability, and depth of invasion may also affect the patient outcome. Recent research development has revealed biological phenotypes of cancer cells to predict the effect of cancer treatment and the clinical course in head and neck cancer. Possible predictive indicators include DNA ploidy, Tpot, EGFR and cyclin D1. C erbB2 and p53 may not predict the survival of patients with head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1996

Endoscopic screening for esophageal cancer in 788 patients with head and neck cancers.

Esophageal cancer has a poor prognosis because it is difficult to detect in its early stages and, even if an operation is possible, the postoperative quality of life is much impaired. An early diagnosis can lead to a good prognosis and enables treatment by endoscopic mucosal resection (EEMR), contributing to a postoperative good quality of life. As head and neck cancers are known to have a high risk of concomitant esophageal cancer, endoscopic screening with iodine staining was performed on 788 patients with head and neck cancers. Among them, 93 cases of esophageal cancers (11.8%) and 23 cases of gastric cancers (2.9%) were detected. Seventy-two cases (77.4%) of the 93 esophageal cancers were superficial cancers limited to the submucosal layer. Twenty cases, treated by EEMR, had a good postoperative course without local recurrence. We suggest that endoscopic screening for esophageal cancer should be performed on all patients with head and neck cancers, because it allows early detection and a good prognosis, and the treatment can be completed by endoscopic maneuver.

Aged↗
PubMed1995

The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer.

The type 1 angiotensin II (AT1) receptor is well characterized but the type 2 (AT2) receptor remains an enigma. We tested the hypothesis that the AT2 receptor can modulate the growth of vascular smooth muscle cells by transfecting an AT2 receptor expression vector into the balloon-injured rat carotid artery and observed that overexpression of the AT2 receptor attenuated neointimal formation. In cultured smooth muscle cells, AT2 receptor transfection reduced proliferation and inhibited mitogen-activated protein kinase activity. Furthermore, we demonstrated that the AT2 receptor mediated the developmentally regulated decrease in aortic DNA synthesis at the latter stages of gestation. These results suggest that the AT2 receptor exerts an antiproliferative effect, counteracting the growth action of AT1 receptor.

Angioplasty, Balloon↗
PubMed1995

The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2.

Angiotensin II type 2 (AT2) receptor is abundantly and widely expressed in fetal tissues but present only in restricted tissues in the adult such as brain and atretic ovary. This receptor is speculated to be involved in tissue growth and/or differentiation. To elucidate the molecular mechanism of growth-regulated AT2 receptor expression, we cloned the mouse AT2 receptor genomic DNA and studied its promoter function in mouse fibroblast-derived R3T3 cells, which express AT2 receptor in the confluent, quiescent state but very low levels of the receptor in actively growing state. Promoter/luciferase reporter deletion analysis of AT2 receptor in R3T3 cells showed that the putative negative regulatory region is located between the positions -453 and -225, which plays an important role in the transcriptional control of AT2 receptor gene expression along with the cell growth. We identified the interferon regulatory factor (IRF) binding motif in this region using DNase foot-printing analysis and demonstrated that IRF binding oligonucleotide treatment increased the AT2 receptor expression in growing R3T3 cells but not in confluent cells. Furthermore, by antisense treatment, we demonstrated that IRF-2 attenuated the AT2 receptor expression in both growing and confluent R3T3 cells, whereas IRF-1 enhanced AT2 receptor expression in the confluent cells only. Consistent with this result, gel mobility shift assay demonstrated that growing R3T3 cells exhibited only IRF-2 binding, whereas confluent cells exhibited both IRF-1 and IRF-2 binding. Furthermore, we observed using reverse transcription-polymerase chain reaction that the IRF-1 mRNA expression was more abundant in confluent cells than growing cells, whereas IRF-2 expression did not change with R3T3 cell growth. We conclude that, in confluent cells, the enhanced expression of IRF-1 antagonizes the IRF-2 effect and increases the AT2 receptor expression. We speculate that these transcriptional factors influence cell growth in part by regulating AT2 receptor expression.

3T3 Cells↗
PubMed1995

Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease.

Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.

Alleles↗
PubMed1995

A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo.

The application of DNA technology to regulate the transcription of disease-related genes in vivo has important therapeutic potentials. The transcription factor E2F plays a pivotal role in the coordinated transactivation of cell cycle-regulatory genes such as c-myc, cdc2, and the gene encoding proliferating-cell nuclear antigen (PCNA) that are involved in lesion formation after vascular injury. We hypothesized that double-stranded DNA with high affinity for E2F may be introduced in vivo as a decoy to bind E2F and block the activation of genes mediating cell cycle progression and intimal hyperplasia after vascular injury. Gel mobility-shift assays showed complete competition for E2F binding protein by the E2F decoy. Transfection with E2F decoy inhibited expression of c-myc, cdc2, and the PCNA gene as well as vascular smooth muscle cell proliferation both in vitro and in the in vivo model of rat carotid injury. Furthermore, 2 weeks after in vivo transfection, neointimal formation was significantly prevented by the E2F decoy, and this inhibition continued up to 8 weeks after a single transfection in a dose-dependent manner. Transfer of an E2F decoy can therefore modulate gene expression and inhibit smooth muscle proliferation and vascular lesion formation in vivo.

Animals↗
PubMed1995

Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

Animals↗