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Biomedical subjects

N Fukai

Publications and source records attributed to N Fukai.

30 records · Page 2Linked to original sources
PubMed1995

Kinetics of 125I-PDGF binding and down-regulation of PDGF receptor in human arterial smooth muscle cell strains during cellular senescence in vitro.

Platelet-derived growth factor (PDGF) is one of the major mitogens in serum to stimulate replication of human smooth muscle cells (SMCs) in culture. Previous studies using human fibroblasts failed to demonstrate changes in the receptor systems for growth factors during cellular senescence. We investigated the kinetics of 125I-PDGF(-BB) binding and down-regulation of the PDGF receptor in three human arterial SMC strains during cellular aging. The number of specific 125I-PDGF binding sites per cell increased slightly at a population doubling level (PDL) of 60%-80% of life span and then decreased at the PDL above 90%. The number of receptors per cell-surface area decreased with increasing in vitro age. The apparent Kd for the 125I-PDGF binding decreased with in vitro senescence. The internalization and degradation of 125I-PDGF per receptor were significantly reduced in senescent SMCs and the amount of 125I-PDGF that escaped degradation and was recycled back to the cell surface was significantly greater in senescent SMCs than young cells. Furthermore, down-regulation of the PDGF receptor was significantly greater in senescent SMCs than young cells. Immunoblot studies demonstrated that changes in beta-subunit of the PDGF receptor accounted for those in the studies using 125I-PDGF and that tyrosine phosphorylation of the PDGF receptor was significantly greater in young SMCs than aged cells. Our results suggest that age-related changes in the receptor systems for PDGF may be important contributors to the failure of DNA synthesis in senescent SMCs.

Arteries↗
PubMed1994

Basement membrane assembly and differentiation of cultured corneal cells: importance of culture environment and endothelial cell interaction.

A three-dimensional corneal tissue construct was used to examine the effect of culture environment and endothelial cell interaction on epithelial differentiation and basement membrane assembly. Rabbit corneal epithelial cells were cultured over rabbit stromal fibroblasts in a collagen matrix with or without an underlying layer of immortalized mouse corneal endothelial cells (Muragaki, Shiota, Inoue, Ooshima, Olsen, and Ninomiya. (1992) Eur. J. Biochem. 207, 895-902). The cultures were grown submerged or at a dry or moist interface. Basement membrane, anchoring fibril, and hemidesmosome assembly was monitored using transmission electron microscopy as well as indirect immunofluorescence microscopy of laminin, type VII collagen, and alpha 6 integrin. Antibodies against keratin 3 (K3) and alpha-enolase marked differentiated and undifferentiated corneal epithelial cells, respectively. When all three cell types were cultured at a moist interface, hemidesmosomes, anchoring fibrils, and a continuous basement membrane were observed 2 wk after lifting the cultures to an air-liquid interface (air-lift). The distribution of alpha-enolase and K3 was identical to patterns seen in the limbal region of the cornea. Air-lifted tissue constructs lacking the endothelial cell layer showed only limited distribution of laminin and type VII collagen at the epithelial-matrix junction. alpha 6 Integrin was present along the entire plasma membrane of the basal cells; epithelial differentiation was not complete as alpha-enolase was seen in basal and two to three layers of suprabasal cells. Submerged cultures without endothelial cells did not express differentiation markers or basement membrane components. These data indicate that endothelial cell interaction dramatically enhances the amount and quality of epithelial basement membrane assembly and that epithelial differentiation is influenced by the type of interface between tissue, liquid, and air.

Animals↗
PubMed1994

Human arterial smooth muscle cell strains derived from patients with moyamoya disease: changes in biological characteristics and proliferative response during cellular aging in vitro.

Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs frequently in children. The etiology is unknown. We examined changes in biological characteristics and responsiveness to serum mitogens during the in vitro cellular aging of arterial smooth muscle cell strains derived from patients with moyamoya disease (HMSMC) and compared them with those of cells from age-matched control patients (HCSMC). HMSMC had a normal human diploid chromosome constitution. HMSMC and HCSMC had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the doubling time at the early passages was significantly longer in moyamoya SMC than control SMC, although there was no significant difference at the late passages. Furthermore, the poor responsiveness of moyamoya SMC to platelet-derived growth factor was retained throughout the life span in vitro. These results support the hypothesis that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.

Adolescent↗
PubMed1993

Kinetics of 125I-PDGF binding and down-regulation of PDGF receptor in arterial smooth muscle cells derived from patients with moyamoya disease.

Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. We recently found that cultured smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease responded poorly to serum mitogens, especially to platelet-derived growth factor (PDGF). In the present study, we investigated further the binding and processing of 125I-PDGF, as well as down-regulation of the PDGF receptor in arterial SMC derived from patients with moyamoya disease. The specific binding sites of 125I-PDGF were reduced significantly at both 4 degrees C and 22 degrees C on SMC from moyamoya disease compared with those from control (4.78 vs. 11.92 x 10(4)/cell at 4 degrees C), though the apparent dissociation constant (Kd) were the same. Kinetics of 125I-PDGF binding at 37 degrees C in cells from moyamoya disease showed fewer binding sites (less than 1/3 of controls) and lower degradation per cell than in those from controls, though no difference was observed in either internalization or degradation of each receptor. When SMC were exposed to lower concentrations of nonlabeled PDGF at 37 degrees C, the percentage of remaining binding sites on cells from moyamoya disease was significantly less than that from controls. This excess down-regulation of PDGF receptor in SMC from moyamoya disease may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These results are closely correlated with the diminished proliferation responses to PDGF in SMC from moyamoya disease and provide evidence that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.

Cell Division↗
PubMed1991

Altered cellular responses to serum mitogens, including platelet-derived growth factor, in cultured smooth muscle cells derived from arteries of patients with moyamoya disease.

Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. The etiology is unknown. We examined cultured arterial smooth muscle cells (SMC) from scalp arteries of five patients with moyamoya disease. In this study we investigated the responsiveness of the cells in culture to serum mitogens including platelet-derived growth factor (PDGF), a major mitogen of SMC, and compared the response to that of cells derived from age-matched control patients. SMC from patients with moyamoya disease proliferated less rapidly in a medium with 15% serum than did control SMC and responded poorly to the addition of PDGF to 5% serum. PDGF alone did not stimulate SMC in a quiescent state to initiate DNA synthesis in moyamoya disease, without serum factors other than bovine serum albumin, though it significantly stimulated the controls. Simultaneous additions of epidermal growth factor, insulin-like growth factor-I, and PDGF stimulated initiation of DNA synthesis in cells from moyamoya disease, but not as much as PDGF alone did in the controls. Although direct correlations with the pathogenesis of the disease remain to be clarified, the results indicate altered interrelations between serum factors and the cellular responses in vessels of moyamoya disease.

Adolescent↗
PubMed1991

[Bacterial meningitis in the elderly with neurosurgical procedures].

Bacterial meningitis is one of complications in the elderly with neurosurgical procedures. In an attempt to find the clinical features of this complication we analyzed 10 cases, which were found in 30 cases of the bacterial meningitis in Tokyo Metropolitan Geriatric Hospital from 1972 to 1989. The patients were 4 males and 6 females, 52-86 years old (the mean, 69). While 2 Enterococcus species were isolated after craniotomy, Staphylococci were common pathogens (4 S. aureus, 4 S. epidermidis and 1 P. aeruginosa) in patients with shunt infection. Most of these patients lacked typical manifestations of meningitis except the fever. Symptoms occurred long after surgery with little abnormality in the data of serum and cerebrospinal fluid. However, blood cultures were positive in 75% of the cases. Removal of the infected catheter was effective in the cases of shunt infection.

Aged↗
PubMed1984

Diagnosis of epidermoid cysts by metrizamide CT cisternography.

The authors describe three cases of intracranial epidermoid cysts specifically diagnosed by metrizamide CT cisternography. In CT cisternography of epidermoid cysts, metrizamide enters deep in the tumor clefts and depicts the lobulated margin of the tumor. We consider these findings are specific for this tumor and similar to the findings reported previously in pneumoencephalography or positive contrast cisternography.

Brain Diseases↗
PubMed1982

Angiographic demonstration of cerebral revascularization after encephalo-duro-arterio-synangiosis (EDAS) performed on pediatric moyamoya patients.

For the treatment of the moyamoya disease, we developed a surgical procedure of Encephalo-duro-aterio-synangiosis (EDAS), which was conducted in 15 cases on 23 sides. As a result we obtained improvement in cerebral vascularization as well as in neurological and electroencephalographic findings in all cases. This report describes an introduction of the procedure and a review of the postoperative cerebral angiograms. Cerebral revascularization by EDAS proceeded on the following steps, and it was confirmed that efficient cerebral revascularization could be obtained 6 months after the operation in almost all cases following the steps: 1) dilatation and increase of dural artery, 2) dilatation of donor scalp artery, 3) cerebral revascularization with the development of visible fine spontaneous anastomoses between the donor scalp artery and the cerebral arteries and 4) further dilatation of the donor scalp artery and retraction of the abnormal rete vasculosum at the base of the brain.

Adult↗
PubMed1981

A new surgical treatment of moyamoya disease in children: a preliminary report.

A new operative method, encephalo-duro-arterio-synangiosis, for the surgical treatment of pediatric moyamoya disease has been developed. The rationale of the operation is to help promote the natural tendency of this disease to develop cerebrovascular collaterals. The method is to transplant a scalp artery with a strip of galea, leaving the distal as well as the proximal arteries intact, to a narrow linear dural opening made under an osteoplastic craniotomy. A representative case is described and the operative procedure is outlined. Our new method is compared with other surgical treatments of this disease.

Arterial Occlusive Diseases↗