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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 19 recordsLinked to original sources

The upstream region of the mouse N-myc gene: identification of an enhancer element that functions preferentially in neuroblastoma IMR32 cells.

The various members of the myc gene family, including c-myc and N-myc, are supposed to play a role in the regulation of cell cycle and proliferation. Whereas c-myc is expressed nearly ubiquitously, the N-myc gene product is found mainly in actively proliferating neural tissues such as early development tissues or in retinoblastomas and neuroblastomas. In this report, the upstream region of mouse N-myc gene was ligated to pSVPCAT, which carries the simian virus 40 (SV40) promoter and bacterial chloramphenicol acetyltransferase (CAT) gene, and transcriptional activities were examined by CAT and S1 protection assays after transfection of the DNAs into human cervical carcinoma HeLa or neuroblastoma IMR32 cells. Several regulatory regions were identified: two promoting regions (-980 to -860 and -279 to +108) and an inhibiting one (-860 to -797). The region spanning positions -980 to -860 increased CAT expression independently of orientation and distance to the SV40 promoter, indicating that the element is a typical enhancer. Moreover, the expression levels from this enhancer were higher in IMR32 cells than in HeLa cells, indicating that action has, if not cell-type specificity, cell-type preference. These findings may provide useful bases for the understanding of the cell-type specific regulation of N-myc expression.

Animals

Stimulation of SV40 DNA replication by the human c-myc enhancer.

In earlier studies we had shown that a transcriptional enhancer sequence exists about 2 kb upstream of the human c-myc gene. The core sequence necessary for enhancer activity was defined therein as a 21 bp nucleotide element, which also showed autonomous replicating activity [EMBO J. (1988) 7, 3135-3142; EMBO J. (1989) 8, 4273-4279]. Recently, several reports have substantiated the notion that transcription and replication can be concertedly regulated in a larger number of cases than expected. In this report, we took the simian virus 40 (SV 40) ori/promoter as a model system. The SV40 enhancer is known to enhance transcription from its ori/promoter, but to reduce its replication (probably due to a negative feedback). The SV40 enhancer was replaced by the c-myc enhancer core in order to see its effect upon SV40 DNA replication and transcription. The results showed that besides stimulating transcription, the c-myc enhancer promoted SV40 DNA replication in monkey CosI cells. Stimulation was only observed when the c-myc enhancer was inserted in the 'up-to-down' orientation to the SV40 promoter. The promoting function of the c-myc enhancer on DNA replication correlated with the transcriptional activation function, as determined by systematic point mutations introduced within the 21 bp core sequence.

Animals

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Adolescent

Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription.

Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of urea cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of urea cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.

Aging

Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice.

Juvenile visceral steatosis (jvs) mice from the C3H-H-2 degrees strain have markedly low levels of all the hepatic urea cycle enzymes (Imamura et al. (1990) FEBS Lett. 260, 119-121). The steady state levels of messenger RNA for the four urea cycle enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the urea cycle enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the urea cycle enzymes but also the regulation of their developmental induction.

Animals

A case of duodenal carcinoma presenting as a submucosal tumor.

This paper describes a patient with duodenal carcinoma showing the features of a submucosal tumor, leading to difficulty in making an accurate preoperative diagnosis. A 63-year-old woman was admitted for investigation of a duodenal mass. An examination of the upper gastrointestinal tract revealed a semicircular compression of the stomach and the duodenum. Endoscopy of the stomach and duodenum disclosed a hemispherical tumor with a deep ulcer in the apex. Computer tomography revealed a tumor of about 5 cm in diameter at the same site. Laparotomy was performed under the tentative diagnosis of a submucosal tumor. A tumor was found occupying the duodenum, which compressed the gastric antrum exteriorly, and was also adherent to the head of the pancreas by direct invasion. A curative resection was performed by combining a pancreatoduodenectomy with a transverse colectomy along with regional lymph node clearance. A microscopic examination showed that the tumor contained neoplastic cells growing in a tubular pattern, particularly in its peripheral regions. Thus, this lesion was finally diagnosed as primary adenocarcinoma of the duodenum.

Adenocarcinoma

Anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract.

A rare case of anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract (AAPBDS without DBT) associated with mucosal dysplasia of the biliary duct is described herein. A 53 year old male with a long history of diarrhea and right upper abdominal pain was diagnosed as having AAPBDS without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y hepatico-jejunostomy was performed and subsequent pathological examination of the surgical specimens showed mucosal hyperplasia of the gall-bladder and mucosal dysplasia of the biliary duct. Considering the dysplastic changes of the biliary duct as seen in our case, and the high incidence of AAPBDS without DBT developing into carcinoma of the biliary duct, being 12.2 per cent, we suggest that pancreaticobiliary ductal diversion with excision of the gallbladder and biliary duct should also be performed for AAPBDS without DBT. However, further pathological investigations concerning the excised biliary duct in AAPBDS without DBT will be need to be carried out.

Bile Ducts

Response of plasma renin-angiotensin system to a single captopril administration in patients receiving long-term treatment with captopril.

1. The responses of angiotensin II (AII), AIII, aldosterone and plasma renin activity (PRA) to a single dose of captopril were investigated in hypertensive patients receiving long-term (more than 1 year) captopril therapy (CT patients) and compared with those of non-treated hypertensive patients (NT patients). 2. Baseline levels of AII and aldosterone were significantly lower in CT patients than in NT patients. AIII tended to be lower and PRA was slightly higher in CT than in NT patients, but these differences were not significant. 3. A single administration of captopril (50 mg orally) significantly decreased plasma levels of AII, AIII and aldosterone as well as blood pressure in both CT and NT patients. 4. These results demonstrate that chronically repeated administration of captopril to hypertensive patients effectively reduces the daily blood pressure and concomitantly the plasma AII level to acceptable levels in patients with no experience of ACE inhibition.

Aldosterone

[Detection and serotyping of HRVs collected from children with acute gastroenteritis in winter of 1986 to 1991].

Fecal samples from sporadic acute gastroenteritis patients who visited at a pediatrician during five consecutive winter seasons in Kurume City located at north part of Kyushu district. Fecal samples were subjected to detection of rotavirus and other viruses and study of yearly changes in serotype of rotavirus. The rate of group A rotavirus positives in third winter and other consecutive winters were 12.5%, 40 to 65%, respectively. 60% specimens were successfully serotyped: 58% was serotype 1.22% was serotype 3.6% was serotype 2, and 14% was serotype 4. The dominant serotype in first, fourth and fifth winter was type 1. However in second winter each serotype of rotavirus was almost equally detected. During five consecutive winters six patients visited at the same pediatrician twice more than two months interval. They all had acute gastrointestinal symptoms. In six patients rotavirus was detective just once.

Acute Disease

Glibenclamide decreases basal coronary blood flow in anesthetized dogs.

The effects of ATP-sensitive K+ channel blockade on coronary blood flow were studied in 13 anesthetized open-chest dogs. A specific ATP-sensitive K+ channel blocker, glibenclamide, was infused into the left circumflex coronary artery (LCx). Coronary blood flow of LCx and systolic segment shortening at the LCx area were measured. Intracoronary infusion of glibenclamide (0.5, 5, and 50 micrograms.kg-1.min-1) decreased coronary blood flow dose dependently. Glibenclamide at the dose of 50 micrograms.kg-1.min-1 decreased LCx coronary blood flow by 55 +/- 4% (P less than 0.01), which was accompanied by a decrease in percentage segment shortening at the LCx area (P less than 0.01) and ST elevation. When coronary blood flow was maintained at the baseline level by simultaneous infusion of sodium nitroprusside (1-3 micrograms/min ic) or pinacidil (0.3-0.6 mg/min ic), glibenclamide did not alter percentage segment shortening or produced ST elevation. The latter results suggest that glibenclamide decreased coronary blood flow, which secondarily induced myocardial ischemia and dysfunction. Our results suggest that ATP-sensitive K+ channels of coronary arteries are involved in maintaining the level of resting coronary blood flow under physiological conditions in anesthetized dogs.

Animals

Effect of L-threo-3, 4-dihydroxyphenylserine on orthostatic hypotension in a patient with spinal cord injury.

A 72-year-old female who underwent the extirpation of metastatic intraspinal tumor showed an extremely wide variation of blood pressure with recurrent episodes of syncope due to paroxysmal hypotension. Treatment of the patient with salt supplement and L-threo-3, 4-dihydroxyphenylserine, an exogenous precursor of norepinephrine, markedly improved the syncopal attack as well as the daily activity.

Adenocarcinoma

Polysplenia syndrome with various visceral anomalies in an adult: embryological and clinical considerations.

A 26-year-old female with polysplenia syndrome is reported. She had numerous visceral anomalies including polysplenia, a short pancreas, a preduodenal portal vein, malrotation of the bowel, azygos continuation of the inferior vena cava, bilateral hyparterial bronchi and symmetrical liver lobation. Embryological and clinical considerations of polysplenia syndrome are described.

Abnormalities, Multiple

Qualitative and quantitative changes in nuclear DNA and phenotypic gene expression in human malignant skin tumors during their progression.

Qualitative and quantitative changes in nuclear DNA and phenotypic expression of human malignant skin tumors were examined during the course of progression. The numerical abnormalities of chromosomes demonstrated by interphase cytogenetics using the chromosome-specific in situ hybridization technique, were also used to reveal qualitative DNA changes in malignant tumor cells. For the analysis of the quantitative changes in nuclear DNA, fluorescence cytophotometry was used on the DAPI-stained tumor cells isolated from the paraffin-embedded sections. To survey abnormal gene expression in malignant tumor cells, lectin histochemistry for different sugar residues, immunohistochemical staining of HLA-DR, and in situ hybridization for H-ras, c-myc, N-myc or v-fos were used. The results showed that: 1) in one case of squamous cell carcinoma with invasion, the number of chromosomal abnormalities was much greater in the invasive than in non-invasive parts, with marked topographical heterogeneities; 2) the DNA-ploidies were largely shifted to the higher side with aneuploid stem-lines and polyploid cells in the invasive parts of all malignant tumors; 3) the expression of HLA-DR was induced at the invasive fronts of malignant melanomas; 4) the GS-I specific sugar residue(D-galactose) appeared in all extra-mammary Paget's cells; and 5) expression of "oncogenes" was found in about 60% of all malignant tumors examined. Thus, the progression of malignancy is accompanied by both qualitative and quantitative changes in nuclear DNA, resulting in abnormal gene expression.

Aneuploidy

A novel class of nuclear RNA (nRNA) with a long life span as a gene repressor candidate.

Different systemic organs of fetal mice were continuously labelled with 5-3H-uridine during the organogenesis periods, and chased for various lengths of time after birth. In the autoradiographs made on paraffin-embedded sections of the organs taken after the chase for longer periods than 1 week, including a 12-months chase, specific labels were present exclusively in all the nuclei. The specific nuclear labels were resistant to RNase A or H digestion and to acid hydrolysis with 1 N HCl at 60 degrees C for 5 min, but were completely abolished by DNase digestion or prolonged acid hydrolysis for 10 min, the optimum condition for the Feulgen reaction to stain DNA. Electrophoretic analysis of the total nucleic acids extracted from the different organs chased for 3 or 12 months showed all the tritium radioactivity to be present in the DNA fraction before digestion with DNase or RNase A, and to be completely absent from the DNA fraction and shifted to the RNA fraction, or to be largely destroyed by degradation, after each digestion, respectively. By HPLC analysis of the total nucleic acid extract after further successive digestions with nuclease P1 and alkaline phosphatase into the constituent nucleotides, it was shown that all tritium activity was incorporated in uridine, without any detectable label in other nucleotides. By the simultaneous labeling of human peripheral lymphocytes at the late S-phase with 5-3H-uridine and BrdU, it was demonstrated that the autoradiographic labels, which, this time, were labile to RNase A digestion, were present in the G-bands of the spread chromosomes as identified by BrdU immunohistochemistry. The findings strongly indicate the presence of a novel class of nuclear RNA (nRNA). This type of RNA (a) may be localized in the nucleus in close association or hybridization with nuclear DNA, (b) have a life span as long as that of the cell, and (c) be duplicated in the late phase of DNA replication. The nRNA may play a fundamental role as gene repressor existing in the G-bands of metaphase chromosomes in the process of ontogeny and cytodifferentiation.

Animals

Importance of acidic mucin secretions by foveolar and mucous neck cells of rat fundic mucosa as the defence mechanisms against HCl as revealed by fasting.

The localization of neutral mucin and acidic mucins in both control and fasted rat gastric fundic mucosa were examined by microscopic and electron microscopic histochemical methods. By Carnoy's fixation, the surface mucous coat of the control rat gastric fundic mucosa was found to be composed of alternating layers of acidic mucins and neutral mucin, indicating the synchronous and cyclic secretions of them. In many gastric pits of the fundic glands, the acidic mucins were found to spring out from the deep foveolar regions like volcanoes. This phenomenon may suggest that the acidic mucins play a fundamental role in protecting the pit cells against HCl during its passage, and the layers of neutral mucin and acidic mucins in the surface coat is the safeguard against the HCl and digestive enzymes in the gastric lumen. In the fasting rat gastric fundic mucosa, the acidity and the amount of the gastric juice were markedly decreased, indicating the suppressed secretions of mucins and HCl. The decreased production of sulfomucin was directly demonstrated by 35SO4-autoradiography. Many mucous neck cells existing in close association with the parietal cells were ballooned due to accumulation of alcian blue (AB)-positive but high iron-diamine (HID)-negative sialomucin, which was not demonstrable in the control. The secretory granules of sialomucin contained in the ballooned mucous neck cells were positively stained ultrastructurally with cacodylate-ferric colloid to stain acid mucopolysaccharides.

Acid Phosphatase