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Biomedical subjects

N Kawada

Publications and source records attributed to N Kawada.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-beta signaling.

Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-beta-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-beta. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-beta-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-beta signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis.

Acid Phosphatase↗
PubMed2005

[Delayed repair for blunt injury of the thoracic aorta complicated with the spinal cord injury; report of a case].

Blunt aortic injury is a major cause of death from blunt trauma and it generally accompanies with the other multiple serious injuries. A 67-year-old man sustained a blunt aortic injury and a fracture of 5th cervical vertebrae complicated with a spinal cord injury. A neurological examination showed a complete paralysis of the limbs. However, his respiratory status and circulatory status were stable. On admission, the paralysis improved resulting from high dose steroid injection and a cervical traction. An orthopedic operation was required before a cardiovascular operation even though computed tomography (CT) showed that a pseudo aortic aneurysm on the distal arch tended to enlarge in the short period. As a result, the aorta was repaired about 5 months after the injury. Delayed repair was performed in safe after careful and serial CT follow-up.

Accidents, Traffic↗
PubMed2005

[Nicks operation for aortic valve dysfunction with pannus formation; report of a case].

A 58-year-old female who underwent an aortic valve replacement 3 years ago was admitted to our hospital. She developed dyspnea in a month. Urgent reoperation was scheduled because an echocardiography demonstrated severe aortic valve regurgitation, and because a cinefluoroscopy showed that a leaflet of the prosthetic valve was restricted. Pannus formation from left ventricular outflow tract caused prosthetic valve insufficiency. An ATS 18 aortic prosthesis was replaced after removing old sewing cuff and surrounding tissue of the aortic annulus as much as possible. However, the coronary orifices were partially covered with the prosthesis. The leaflet rubbed onto the left ventricular outflow muscle specially in opening position. Therefore, an annular enlargement was required. In case of re-replacement of prosthetic valve for small aortic annulus, the annulus was at most same size or smaller than it of the previous operation. It was harmful for the patient whose body surface area was 1.74 m2 to utilize smaller prosthesis because of patient-prosthesis mismatch. We conclude that annular enlargement is useful for reoperarion of small aortic annulus associate with left ventricular outflow hypertrophy.

Aortic Valve↗
PubMed2004

Identification and mapping of cleistogamy genes in barley.

Cleistogamy is a closed type of flowering with ensured self-pollination and an important trait to study evolutionary development in flower organs, reproduction systems, gene flow, and disease control. Still, very limited information is available about the genetic control and regulatory mechanism of this trait in barley. In this work, from the eight crosses between cleistogamous and chasmogamous accessions, five crosses generated chasmogamous F1 plants and their F2 plants segregated as 3 chasmogamous:1 cleistogamous, whereas three crosses generated cleistogamous F1 plants, and their F2 plants segregated as 1 chasmogamous:3 cleistogamous. Although a single gene was responsible for the control of cleistogamy in these two groups of crosses, the direction of dominance was opposite, suggesting two genes, cly1 and Cly2, for the genetic control of cleistogamy in barley. Epistatic type of gene interaction between the two loci was detected. In the analysis of 99 recombinant inbred lines of 'Azumamugi' x 'Kanto Nakate Gold' and doubled haploid lines of 'Harrington' x 'Mikamo Golden', where in both crosses F1 was chasmogamous, the cly1 locus has been mapped on chromosome 2HL. Using the analysis of the F2 population of 'Misato Golden' and 'Satsuki Nijo' where F1 was cleistogamous, the Cly2 locus was mapped in the same region of chromosome 2HL. Because the cly1 and Cly2 loci were mapped in the same region in these three different mapping populations, it was concluded that the expression of cleistogamy is under the control of two tightly linked genes or different alleles of the same gene.

Chromosome Mapping↗
PubMed2004

[Successful repair of the left ventricular wall rupture after mitral valve replacement of an octogenarian; report of a case].

The left ventricular wall rupture is not only a rare complication after mitral valve replacement, but also a high mortality disease. We have encountered a case of this complication after removal of the extracorporeal circulation in an octogenarian female after mitral valve replacement with Carpentier-Edwards (25 mm). It could be successfully repaired from outside the heart on the cardiopulmonary bypass without second cardiac arrest. Repair from inside the heart using extracorporeal circulation and cardioplesia is generally recommended because of the accuracy. However, second cardiac arrest might be a risk of postoperative complications in octogenarians. Hence, prevention is the most important. And operative strategy for the repair is also important in these patients.

Aged↗
PubMed2002

An arming yeast with the ability to entrap fluorescent 17beta-estradiol on the cell surface.

We constructed a novel surface-engineered yeast displaying the ligand-binding domain of the rat estrogen receptor (ERLBD). ERLBD, display of which on the yeast cell surface was confirmed by immunofluorescence, possessed strong binding activity to fluorescent 17beta-estradiol - an analogue of the natural ligand of the estrogen receptor - that was comparable to the activity of the native receptor. Environmental homeostasis has recently been disturbed by endocrine disruptors, which cause confusion in the hormone secretion system. It is therefore very important to identify chemical compounds with hormone-like activity and remove them from the environment. The present results demonstrate that the new arming yeast displaying ERLBD on its cell surface will be capable of screening, entrapping, and removing estradiol-like compounds from the environment.

Animals↗
PubMed2002

The hepatic stellate cell in the post-genomic era.

The draft human genome sequence was published on February 15, 2001, which will provide a huge amount of information on human genetics, human disease, and human cell biology. Now, medical scientists and cell biologists are turning their attention to illustrating gene expression pattern using gene microarray and to identifying the functions and the expression patterns of proteins encoded by the genes. Hepatic stellate cell is one of the sinusoid-constituent cells that play multiple roles in the liver pathophysiology. Transformation of stellate cells from the vitamin A-storing phenotype to the "myofibroblastic" one closely correlates to hepatic fibrosis during chronic liver trauma. Analyses of the molecular mechanisms of stellate cell activation have made a great progress, in particular, in the field of intracellular signal transduction of transforming growth factor-beta and platelet-derived growth factor, integrin signaling related to cell-adhesion, and cell motility-associated Rho and focal-adhesion kinase. Accumulation of the information on the stellate cell activation would shed light on the establishment of a novel therapeutic strategy against fibrosis of human liver disease.

Animals↗
PubMed2002

[A successful surgical treatment for original Taussig-Bing malformation 13 years after banding of the pulmonary artery].

A 13-year-old girl with original Taussig-Bing malformation underwent successful intraventricular rerouting. In this congenital heart disease, the large pulmonary flow elevates pulmonary arterial pressure and progress the pulmonary vascular diseases in early infancy. Banding of the pulmonary artery helps to prevent the irreversible vascular changes, while that may result in further hypertrophy of the right ventricle. Ideally, radical repair should be performed as soon as possible after definitive diagnosis. Although, she had banding operation of the pulmonary artery at 8 months of age, there was no difference between the right ventricle and the aortic pressure. The subpulmonary space was large enough to make the tunnel with an internal conduit. Additionally, right ventricle outflow tract reconstruction was performed by a Dacron patch. The postoperative cathetherization demonstrated no stenotic region in both left and right ventricular outflow tract. The Kawashima intraventricular rerouting can be applied to the patients without the subaortic stenosis if banding of the pulmonary artery have been performed long before.

Adolescent↗
PubMed2001

Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta.

Redox-regulated processes are important elements in various cellular functions. Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal transduction and cell growth through their radical scavenging action. However, recent studies have shown that reactive oxygen species are not always involved in ligand-stimulated intracellular signaling. Here, we report a novel mechanism by which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular smooth muscle cells, we found that reducing agents, including NAC, triggered extracellular proteolysis of PDGF receptor-beta, leading to desensitization of hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted mature cathepsin B. In addition, type II transforming growth factor-beta receptor was also down-regulated. Furthermore, these events seemed to cause a dramatic improvement of rat liver fibrosis. These results indicated that redox processes impact the cell's response to growth factors by regulating the turnover of growth factor receptors and that "redox therapy" is promising for fibrosis-related disease.

Animals↗
PubMed2001

Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells.

A proteome approach for the molecular analysis of the activation of rat stellate cell, a liver-specific pericyte, led to the discovery of a novel protein named STAP (stellate cell activation-associated protein). We cloned STAP cDNA. STAP is a cytoplasmic protein with molecular weight of 21,496 and shows about 40% amino acid sequence homology with myoglobin. STAP was dramatically induced in in vivo activated stellate cells isolated from fibrotic liver and in stellate cells undergoing in vitro activation during primary culture. This induction was seen together with that of other activation-associated molecules, such as smooth muscle alpha-actin, PDGF receptor-beta, and neural cell adhesion molecule. The expression of STAP protein and mRNA was augmented time dependently in thioacetamide-induced fibrotic liver. Immunoelectron microscopy and proteome analysis detected STAP in stellate cells but not in other hepatic constituent cells. Biochemical characterization of recombinant rat STAP revealed that STAP is a heme protein exhibiting peroxidase activity toward hydrogen peroxide and linoleic acid hydroperoxide. These results indicate that STAP is a novel endogenous peroxidase catabolizing hydrogen peroxide and lipid hydroperoxides, both of which have been reported to trigger stellate cell activation and consequently promote progression of liver fibrosis. STAP could thus play a role as an antifibrotic scavenger of peroxides in the liver.

Amino Acid Sequence↗
PubMed2001

Effect of breath holding on blood flow measurement using fast velocity encoded cine MRI.

Breath-hold MR measurement of cardiac output was compared with results from respiratory triggered MR acquisitions, since flow measurement during breath-holding may be different from physiological blood flow. Cardiac output during large lung volume breath-holding (4.47 +/- 0.63 l/min in the aorta and 4.53 +/- 0.59 l/min in the pulmonary artery) was significantly lower than that measured during normal breathing (6.09 +/- 0.49 l/min and 6.48 +/- 0.67 l/min, P < 0.01). In contrast, no significant difference was found between measurements conducted with small lung volume breath-holding (5.87 +/- 0.53 l/min and 6.41 +/- 0.75 l/min) and normal breathing. In conclusion, breath-hold MR flow measurement using small lung volume by shallow inspiration can provide a blood flow quantification that is close to physiological blood flow. Magn Reson Med 45:346-348, 2001.

Adult↗
PubMed2001

Right ventricular dynamic cardiomyoplasty for the univentricular heart with pulmonary hypertension.

OBJECTIVES: We conducted an acute experimental study to test the feasibility of dynamic cardiomyoplasty in a setting of modified Fontan procedure for univentricular heart with pulmonary hypertension to obtain a possible proxy for high-risk Fontan candidates. METHODS: After electrical preconditioning of the left latissimuss dorsi for 6 weeks in 8 dogs, the right ventricular cavity was totally obliterated with concomittent closure of the tricuspid valve and right pulmonary artery. Modified Fontan circulation was established with the aortic homograft anastomosed between the right atrium and pulmonary trunk, incorporated with a pericardial pouch as a compression chamber (neoright ventricle) fixed onto the epicardial surface of the ventricle. After cardiopulmonary bypass termination, a latissimus dorsi was applied to wrap the pericardial pouch and ventricle clockwise and stimulated with a trained-pulse (25 Hz) at 1:1 synchronization ratio with cardiac beats. RESULTS: Profound right heart failure was noted during Fontan circulation in increased pulmonary vascular resistance (11 +/- 3.2 Wood units), whereas graft pacing showed significant augmentation of systolic pulmonary pressure by 54 +/- 12%, the mean pulmonary flow by 68 +/- 23%, and aortic pressure by 23 +/- 5% at a physiological range of central venous pressure (13.2 +/- 0.7 mmHg). Right heart function curve analysis confirmed marked augmentation of right heart performance, restoring almost normal pulmonary circulation. These functional benefits were sustained up to 4 hours in 4 animals until experiments were terminated. CONCLUSIONS: Dynamic cardiomyoplasty in a modified Fontan procedure is a viable surgical option for univentricular heart, not a Fontan candidate.

Animals↗
PubMed2001

Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction.

BACKGROUND: Recently, we demonstrated increased oxidative stress in the interstitium of ureteral obstructed kidneys based on the increased expression of heme oxygenase-1 and immunohistochemical detection of advanced glycation end products (AGE) in the interstitium. Antioxidant therapy may have a therapeutic potential toward interstitial fibrosis of unilateral ureteral obstruction (UUO) kidneys. Fluvastatin is an HMG-CoA reductase inhibitor and has been demonstrated to have an antioxidant activity in vitro. METHODS: The effects of fluvastatin on UUO kidneys from the viewpoints of antioxidant action in vivo and antifibrosis action were studied. To investigate the antioxidant action and its therapeutic efficacy of fluvastatin in UUO kidneys, AGE accumulation and fibrosis in the obstructed kidneys was compared among vehicle-, pravastatin-, or fluvastatin-treated (10 or 40 mg/kg/day) groups. RESULTS: Tubulointerstitial fibrosis was significantly attenuated in fluvastatin-treated animals. Fluvastatin significantly suppressed the degree of immunostaining of AGE in UUO kidneys. CONCLUSIONS: These results provide evidence for the antioxidant action of fluvastatin in vivo. The decreased interstitial fibrosis along with a decreased oxidative stress marker in the interstitial lesion strongly suggests the existence of a causal relationship between them. Fluvastatin may have therapeutic value in slowing or preventing interstitial fibrosis in progressive renal disease.

Actins↗