Biomedical subjects

S Yamanaka

Publications and source records attributed to S Yamanaka.

At least 19 recordsLinked to original sources

PubMed2000

Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway.

NAT1/p97/DAP5 is a newly identified protein that shares homology with the translation initiation factor eIF4G. Studies in vitro and in transfected cells indicated that NAT1 might suppress global translation, thereby repressing cellular proliferation. Here we studied the functions of NAT1 in vivo by disrupting its gene in mice. NAT1(-/-) embryos died during gastrulation, indicating a crucial role for NAT1 in embryogenesis. Undifferentiated NAT1(-/-) embryonic stem cells were normal in morphology, proliferation, global translation and gene expression profile. However, NAT1(-/-) cells exhibited an impaired ability to differentiate: they were resistant to differentiation induced by retinoic acid, and teratomas derived from them consisted of undifferentiated and poorly differentiated tissues. The expression of retinoic acid-responsive genes, such as the cell-cycle inhibitor p21(WAF1), was selectively impaired in NAT1(-/-) cells. Transcription from synthetic retinoic acid-responsive elements was also impaired. These data demonstrated that this translation initiation factor homolog controls specific gene expression pathways required for cellular differentiation.

Animals↗

PubMed2000

Evolution, structure, and expression of GNPI/Oscillin orthologous genes.

Oscillin was identified from hamster sperm as a factor responsible for oocyte calcium oscillations. However, its high level of homology with the bacterial glucosamine-6-phosphate isomerase suggests that it may play more fundamental roles. In the current study, we identified Oscillin orthologs from Caenorhabditis elegans, Drosophila melanogaster, mouse, and human. Their amino acid identities with hamster oscillin were 67.0, 72.3, 97.6, and 95.5%, respectively. No Oscillin orthologs were found in Saccharomyces cerevisiae. The human Oscillin gene (HGMW-approved symbol GNPI) spans 12.4 kb and consists of eight exons. The position of the fourth intron was conserved in other species. The human Oscillin promoter has features characteristic of housekeeping genes, including a GC-rich content, multiple SP1 binding sites, and the absence of a TATA motif. Human and mouse Oscillin genes were ubiquitously expressed in all tissues examined. These data showed that Oscillin is a housekeeping gene conserved throughout evolution and do not support the notion that Oscillin is the sperm-specific factor responsible for calcium oscillations.

Aldose-Ketose Isomerases↗

PubMed2000

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Adenocarcinoma↗

PubMed2000

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.

Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

Adult↗

PubMed2000

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Adult↗

PubMed2000

Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations in systemic hemodynamics in rats.

The present experiments were conducted to clarify the mode of cardiovascular action of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a nitric oxide (NO) scavenger, during rat endotoxic shock by determining cardiac output and systemic arterial tone simultaneously. Lipopolysaccharide (LPS) (10 mg/kg, i.v.) decreased systemic blood pressure and cardiac output with transient increases in hematocrit and total vascular resistance. Administration of carboxy-PTIO (1.7 mg x kg(-1) x min(-1), i.v. for 60 min) at 90 min after LPS attenuated further decline in blood pressure and cardiac output without affecting changes in hematocrit or total vascular resistance. It is concluded that carboxy-PTIO attenuates endotoxin-induced hypotension predominantly by maintaining cardiac output in rat experimental endotoxic shock.

Animals↗

PubMed2000

Chromosome 22q11 deletion complicated by dissecting pulmonary arterial aneurysm and jejunal atresia in an infant.

We present an autopsy case of a 46-day-old male infant with chromosome 22q11 deletion, which is considered the primary cause of several diseases, including DiGeorge syndrome and velocardiofacial syndrome. The patient had 2 notable congenital abnormalities: multiple dissecting pulmonary arterial aneurysms distributed in both lungs and multiple jejunal atresia with apple-peel deformity. The former, a very rare pathologic condition especially in infancy, was found incidentally at autopsy and was the primary cause of death. To our knowledge, neither of these lesions has been reported previously in a patient with chromosome 22q11 deletion.

Aortic Dissection↗

PubMed2000

[A case of synchronous ipsilateral renal cell carcinoma and ureteral transitional cell carcinoma].

A 62-year-old man was admitted to our hospital with the chief complaint of right flank pain. Abdominal computed tomographic scan revealed a right hydronephrosis and intrapelvic tumor. Ultrasound revealed a renal mass lesion. Ultrasound guided renal biopsy and laparotomy of intrapelvic tumor was performed. The histopathological diagnosis was renal cell carcinoma and ureteral transitional cell carcinoma.

Biopsy↗

PubMed2000

[Cracks of polycarbonate three-way stopcock are caused by fat emulsion not by propofol].

We found fine cracks in a three-way stopcock after continuous infusion of propofol (Diprivan, Astra-Zeneca, UK). In this paper the possible mechanism was investigated. At first we checked various three-way stopcocks of various manufactures, such as JMS, Terumo, Nipro and Top. All of them were made with polycarbonate. Fine cracks were observed in all stopcocks after 6 hours of liquid contact with propofol between the three-way stopcock and male connector. Based on the mechanical stretch tests of polycarbonate plastic strips with saline, 10% fat emulsion (Intralipid, Otsuka, Japan), or 1% propofol in 10% fat emulsion (Diprivan), significantly greater cracks were observed in both fat group and propofol group, compared with the saline group. But there was no significant difference in cracks between fat and propofol groups. The size of crack increased in a time and strength dependent manner. We conclude that the cause of cracks in three-way stopcock is fat emulsion as a vehicle of propofol not propofol itself.

Anesthesiology↗

PubMed1999

Tissue distribution of placenta-type 6-phosphofructo- 2-kinase/fructose-2,6-bisphosphatase.

Several isozymes of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase have been characterized from mammalian tissues and, based on tissue origin, they are classified as liver, skeletal muscle, heart, testis, and placenta isozymes. In this paper, we examined the tissue distribution of placenta-type isozyme in rat tissues at the levels of transcription and translation. Analysis by Northern blotting showed that placenta, brain, testis, liver, kidney, and skeletal muscle expressed mRNA of placenta-type isozyme. Western blot analysis of fractions from POROS-HQ column chromatography of extracts from various rat tissues showed that proteins of placenta-type isozyme are expressed in placenta, brain, testis, liver, spleen, heart and lung, but not in kidney and skeletal muscle. An immunohistochemical study showed that, in liver, placenta-type isozyme is localized in Kupffer cells. These results indicate that isozymes of this particular enzyme may occur in particular cell types within each tissue.

Animals↗

PubMed1999

Noonan syndrome and cavernous hemangioma of the brain.

We present two patients with multiple characteristics that occur in Noonan phenotype and cavernous hemangioma of the brain. The first patient, who had been diagnosed radiographically as having a cavernous hemangioma in the left basal ganglia at age 15 years, developed massive intracerebral hemorrhage, resulting in sudden death at home at 19 years. The second patient, who was diagnosed radiographically as having a cavernous hemangioma in the left parietal lobe at age 17 years, is being followed carefully (the patient is currently 18 years old). A review disclosed four cases of structural cerebrovascular abnormalities with or without subsequent hemorrhage. Neither these four patients nor our two patients had any severe anomalies in the heart or large vessels, which are frequently seen in patients with Noonan syndrome. Cerebrovascular abnormalities might have a significant influence on the prognosis of patients with Noonan syndrome, especially those having no severe abnormalities in the heart or large vessels.

Adolescent↗

PubMed1999

Conversion of brain-specific complex type sugar chains by N-acetyl-beta-D-hexosaminidase B.

The N-linked sugar chains, GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-4)(Manalpha1++ +-3)Manbeta1-4GlcNAcb eta1-4(Fucalpha1-6)GlcNAc (BA-1) and GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-4)(GlcNAcbeta1 -2Manalpha1-3)Manb eta1-4GlcNAcbeta1-4(Fucalpha1-6)GlcNAc (BA-2), were recently found to be linked to membrane proteins of mouse brain in a development-dependent manner [S. Nakakita, S. Natsuka, K. Ikenaka, and S. Hase, J. Biochem. 123, 1164-1168 (1998)]. The GlcNAc residue linked to the Manalpha1-3 branch of BA-2 is lacking in BA-1 and the removal of this GlcNAc residue is not part of the usual biosynthetic pathway for N-linked sugar chains, suggesting the existence of an N-acetyl-beta-D-hexosaminidase. Using pyridylaminated BA-2 (BA-2-PA) as a substrate the activity of this enzyme was found in all four subcellular fractions obtained. The activity was much greater in the cerebrum than in the cerebellum. To further identify the N-acetyl-beta-D-hexosaminidase, BA-1 and BA-2 in brain tissues of Hex gene-disrupted mutant mice were detected and quantified. PA-sugar chains were liberated from the cerebrum and cerebellum of the mutant mice by hydrazinolysis-N-acetylation followed by pyridylamination. PA-sugar chains were separated by anion-exchange HPLC, size-fractionation, and reversed-phase HPLC. Each peak was quantified by measuring the peaks at the elution positions of authentic BA-1-PA and BA-2-PA. BA-2-PA was detected in all the PA-sugar chain fractions prepared from Hexa, Hexb, and both Hexa and Hexb (double knockout) gene-disrupted mice, but BA-1 was not found in the fractions from Hexb gene-disrupted and double knockout mice. These results indicate that N-acetyl-beta-D-hexosaminidase B encoded by the Hexb gene hydrolyzed BA-2 to BA-1.

Animals↗

PubMed1999

Contribution of extracellular signal-regulated kinase to angiotensin II-induced transforming growth factor-beta1 expression in vascular smooth muscle cells.

We have previously demonstrated that angiotensin II (Ang II) contributes to the increase in aortic transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in hypertensive rats. However, the molecular mechanism whereby Ang II promotes TGF-beta(1) expression in vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the role of extracellular signal-regulated kinase (ERK) in Ang II-mediated TGF-beta(1) expression in VSMCs and the role of Ang II in aortic ERK activity of stroke-prone spontaneously hypertensive rats. Treatment of quiescent VSMCs with 100 nmol/L Ang II induced rapid phosphorylation and activation of ERK1 and ERK2 with a peak at 5 minutes followed by an increase in activator protein-1 (AP-1) DNA binding activity, as shown by gel mobility shift assay. An increase in TGF-beta(1) mRNA was shown by Northern blot analysis. Treatment of VSMCs with PD98059, a specific inhibitor of the ERK pathway, attenuated both the activation of AP-1 and the increase in TGF-beta(1) mRNA induced by Ang II. Inhibition of Ang II-induced AP-1 activation with c-fos antisense oligodeoxynucleotide led to a significant reduction of TGF-beta(1) mRNA in VSMCs. Furthermore, in vivo treatment of stroke-prone spontaneously hypertensive rats with losartan, an Ang II type 1 receptor antagonist, decreased aortic ERK activity. Thus, we show that ERK, through AP-1 activation, is involved in Ang II-induced TGF-beta(1) mRNA expression in VSMCs and suggest that ERK may participate in vascular remodeling of hypertension. However, it remains to be determined whether the increase in TGF-beta(1) mRNA leads to the increase in its active protein.

Angiotensin II↗

PubMed1999

Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs.

Direct effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 microg x kg(-) x min (-1)), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect.

Adenosine↗

PubMed1999

No participation of adenosine A1 receptor in acute nephrotoxicity by 4-pentenoic acid administration in dogs.

Intrarenal infusion of 4-pentenoic acid is known to lower renal cortical ATP content and cause a reduction in glomerular filtration rate (GFR). The alteration in nucleotide metabolism might augment the production of adenosine, thereby eliciting the fall in GFR. This study was conducted to examine whether 4-pentenoic acid stimulates renal production of adenosine, and if so, to examine the role of adenosine A1 receptor in the reduction of GFR by 4-pentenoic acid. With infusion of 4-pentenoic acid (1 micromol x kg(-1) x min(-1)) into the renal artery of anesthetized dogs, GFR gradually decreased and reached minimum at 60 min with values ranging from 33.9+/-2.2 to 20.2+/-2.8 ml/min. Neither renal blood flow nor mean arterial pressure was affected, but tubular reabsorption of water and sodium was significantly attenuated. Renal venous plasma concentration and urinary excretion of adenosine rose markedly (20-fold) without any change in arterial concentration, suggesting that renal adenosine production was augmented by 4-pentenoic acid. However, KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a selective antagonist of the adenosine A1 receptor, did not affect the action of 4-pentenoic acid on GFR or renal handling of water and sodium. It is concluded that 4-pentenoic acid markedly increases renal adenosine production, but adenosine A1 receptor is not involved in the 4-pentenoic acid-induced nephrotoxicity.

Acute Kidney Injury↗

PubMed1998

Isolation of myxobacteria from the marine environment.

In an attempt to isolate indigenous marine myxobacteria from coastal samples, we obtained two swarm forming bacteria. Both isolates formed cell aggregates which, at least in one isolate, developed to fruiting body-like structures consisting of a mass of myxospore-like cells. The optimum NaCl concentrations for their growth were between 2 and 3%, comparable to the NaCl concentration of seawater. This growth characteristic strongly suggests that the two isolates are specific marine bacteria. The 16S rDNA sequence studies indicated that the two isolates were related to the genus Nannocystis. Based on the phylogenetic distances between branches, we concluded that the isolates should be assigned to two new myxobacterial genera.

Culture Media↗

PubMed1998

The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile.

LOX-1 is an endothelial receptor for oxidized low-density lipoprotein that plays essential roles in atherogenesis. LOX-1 has the highest homology with C-type lectin receptors expressed on natural killer cells. In the present study, we cloned and characterized the human LOX-1 gene (HGMW-approved symbol OLR1). The gene structure of LOX-1 resembles that of the natural killer cell receptors. Fluorescence in situ hybridization and analyses of a yeast artificial chromosome contig revealed that the human LOX-1 gene is located in the natural killer gene complex on chromosome 12p12-p13, where the genes of the natural killer cell receptors cluster. In contrast, the expression pattern of LOX-1 is different from that of the natural killer cell receptors; LOX-1 is expressed in vascular-rich organs, but not in lymphocytes. A 1753-bp fragment of the 5' flanking region of the LOX-1 gene had a functional promoter activity. This region contains binding sites for several transcription factors, including the STAT family and NF-IL6, and the expression of LOX-1 was upregulated by several cytokines. These results demonstrate that the human LOX-1 gene is a new member of the natural killer gene complex with a unique expression profile.

Amino Acid Sequence↗

PubMed1998

Differential activation of cardiac c-jun amino-terminal kinase and extracellular signal-regulated kinase in angiotensin II-mediated hypertension.

Two subgroups of mitogen-activated protein kinases, c-jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), are thought to be involved in cultured cardiac myocyte hypertrophy and gene expression. To examine the in vivo activation of these kinases, we measured cardiac JNK and ERK activities in conscious rats subjected to acute or chronic angiotensin II (Ang II) infusion, by using in-gel kinase methods. About 50 mm Hg rise in blood pressure by Ang II (1000 ng . kg-1 . min-1) infusion caused larger activation of left ventricular JNK than ERK, via the AT1 receptor. In spite of short duration (about 30 minutes) of maximal blood pressure elevation by Ang II, JNK sustained the peak value (more than 5-fold increase) from 15 minutes up to at least 3 hours. Similar activation of JNK was seen in the right ventricle. Thus, cardiac JNK activation by Ang II seems to be in part mediated by its direct action via the AT1 receptor. The dose-response relationships for Ang II-induced rises in blood pressure and cardiac JNK and ERK activation indicated that cardiac JNK or ERK was not activated by a mild increase in blood pressure and that cardiac JNK was activated by Ang II-mediated hypertension in a more sensitive manner than ERK. Cardiac hypertrophy, induced by chronic Ang II infusion, was preceded by JNK activation without ERK activation. Furthermore, gel mobility shift analysis showed that cardiac JNK activation was followed by increased activator protein-1 DNA binding activity due to c-Fos and c-Jun. These results provided the first evidence for the preferential activation of cardiac JNK in Ang II-induced hypertension and suggested that JNK might play some role in Ang II-induced cardiac hypertrophic response in vivo. However, further study is needed to elucidate the role of JNK in cardiac hypertrophy in vivo.

Analysis of Variance↗