Biomedical subjects

M Aoyagi

Publications and source records attributed to M Aoyagi.

At least 19 recordsLinked to original sources

PubMed1999

GT1b in human metastatic brain tumors: GT1b as a brain metastasis-associated ganglioside.

We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.

Adenocarcinoma↗

PubMed1998

1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency.

The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analog N-phosphonacetyl-L-ornithine has been solved at 1.85-A resolution by molecular replacement. Deleterious mutations produce clinical hyperammonia that, if untreated, results in neurological symptoms or death (ornithine transcarbamylase deficiency). The holoenzyme is trimeric, and as in other transcarbamoylases, each subunit contains an N-terminal domain that binds carbamoyl phosphate and a C-terminal domain that binds L-ornithine. The active site is located in the cleft between domains and contains additional residues from an adjacent subunit. Binding of N-phosphonacetyl-L-ornithine promotes domain closure. The resolution of the structure enables the role of active site residues in the catalytic mechanism to be critically examined. The side chain of Cys-303 is positioned so as to be able to interact with the delta-amino group of L-ornithine which attacks the carbonyl carbon of carbamoyl phosphate in the enzyme-catalyzed reaction. This sulfhydryl group forms a charge relay system with Asp-263 and the alpha-amino group of L-ornithine, instead of with His-302 and Glu-310, as previously proposed. In common with other ureotelic ornithine transcarbamoylases, the human enzyme lacks a loop of approximately 20 residues between helix H10 and beta-strand B10 which is present in prokaryotic ornithine transcarbamoylases but has a C-terminal extension of 10 residues that interacts with the body of the protein but is exposed. The sequence of this C-terminal extension is homologous to an interhelical loop found in several membrane proteins, including mitochondrial transport proteins, suggesting a possible mode of interaction with the inner mitochondrial membrane.

Amino Acid Sequence↗

PubMed1998

Decrease in p53 protein in cultured cardinal ligament fibroblasts from patients with prolapsus uteri.

The authors examined the growth response of cardinal ligamental fibroblasts derived from patients with prolapsus uteri (HPLiF) and compared it with the response of those from control subjects (HCLiF). The growth rate during the logarithmic growth phase was not different between HPLiF and HCLiF, while the cell density at confluence (saturation density) was significantly higher in HPLiF than in HCLiF. When added alone, platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-I), and epidermal growth factor (EGF) produced minimal effects on DNA synthesis in HCLiF. The simultaneous addition of PDGF, IGF-I and EGF synergistically stimulated the DNA synthesis. In contrast, PDGF alone was able to initiate DNA synthesis in HPLiF. The combination of PDGF, IGF-I, and EGF significantly stimulated the DNA synthesis of HPLiF compared with HCLiF. p53 protein and p53 gene transcripts decreased by 50% in HPLiF. The anti-WAF1 antibody reacted intensely with a 21-kDa protein in the homogenates of control fibroblasts, while the immunoreactive band in prolapsus fibroblasts was clearly reduced. These results indicate that the higher proliferative activity at near confluency in prolapsus fibroblasts may result from the decreased expression of p53 protein and p53 mRNA followed by the decrease in p21 protein. Furthermore, the failure of cells to enter quiescence may lead to a decrease in the synthesis and deposition of elastin and thus may contribute to the loss of supportive function in uterine connective tissues.

Aged↗

PubMed1998

Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation.

Extracellular matrix-degrading enzymes may play a key role in vascular remodeling after arterial wall injury. We investigated the immunolocalization of matrix metalloproteinases (MMPs) in rabbit carotid arteries after balloon denudation. Positive immunostaining for MMP-1, -2, -3, and -9 appeared through the neointima 1 week after balloon denudation. The localization of immunopositive smooth muscle cells (SMCs) for MMP- 1, -3, and -9, particularly for MMP-9, was almost similar to that of replicative SMCs and became confined to the luminal surface layer of the neointima at later time periods. However, MMP-2-positive SMCs appeared also in the basal layer of the neointima at 2 weeks, increased at 4 weeks, and then totally occupied the neointima at 6 weeks. The MMP-2-positive SMCs in the basal layer of the neointima at 4 and 6 weeks were negative for proliferation-associated antigens and were surrounded by extracellular matrix proteins. Our results suggest that all MMPs act in coordination to promote replication and migration of SMCs in the earlier phases of neointimal formation and that MMP-2 independently contributes to the later stages by facilitating the migration but not replication of SMCs from the media to the intima.

Animals↗

PubMed1998

Recurrence in meningeal hemangiopericytomas.

BACKGROUND: Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial. CASE DESCRIPTION: We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors. CONCLUSIONS: Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.

Adult↗

PubMed1998

Differences in cellular responses to mitogens in arterial smooth muscle cells derived from patients with moyamoya disease.

BACKGROUND AND PURPOSE: Moyamoya disease is a progressive cerebrovascular occlusive disease affecting primarily children. The etiology remains unknown. We examined the chemotactic and proliferative activities of inflammatory cell products from arterial smooth muscle cells (SMCs) derived from moyamoya patients and compared them with those from control subjects. METHODS: We used 12 SMC strains from moyamoya patients and eight from control subjects. SMC migration was examined in a micro chemotaxis chamber. DNA synthesis was measured by an immunoperoxidase technique. RESULTS: Platelet-derived growth factor (PDGF)-BB markedly stimulated cell migration and DNA synthesis in control SMCs. PDGF-AA stimulated only DNA synthesis in control SMCs. In moyamoya SMCs, PDGF-AA and PDGF-BB stimulated cell migration but not DNA synthesis. Basic fibroblast growth factor had little migratory activity but stimulated DNA synthesis in moyamoya SMCs and control SMCs. Conversely, hepatocyte growth factor stimulated cell migration but not DNA synthesis in moyamoya SMCs and control SMCs. In contrast, interleukin-1 beta (IL-1 beta) significantly stimulated the migration and DNA synthesis of control SMCs, while it inhibited moyamoya SMC migration. The levels of IL-1 beta-induced nitric oxide production did not differ between moyamoya SMCs and control SMCs, suggesting that IL-1 beta inhibits the migration of moyamoya SMCs through a nitric oxide-independent pathway. CONCLUSIONS: The differences in responses to PDGF and IL-1 in moyamoya SMCs are involved in the mechanism by which intimal thickening develops in moyamoya disease.

Anticoagulants↗

PubMed1998

[A case of orbital mesenchymal chondrosarcoma].

A 22-year-old male presented with proptosis of his right eye of one month's duration. No abnormalities were present regarding visual acuity, ocular motility, or fundus findings. Systemic examinations gave negative results. An orbital tumor, 25 mm in size, was detected by computed tomography and magnetic resonance imaging in the affected side. The tumor was located nasal-posterior to the eyeball and appeared to be in apposition with the orbital floor. The tumor was removed through a maxillary sinus approach. Histopathological studies led to the diagnosis of extraskeletal mesenchymal chondrosarcoma. To the best of our knowledge, this is only the fifth case reported in Japan of mesenchymal chondrosarcoma. Originating in the orbit.

Adult↗

PubMed1998

[Hodgkin's disease].

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Decrease in elastin gene expression and protein synthesis in fibroblasts derived from cardinal ligaments of patients with prolapsus uteri.

Abnormal connective tissues may be a key factor in the development of pelvic supportive disorders. Elastin gene transcripts and elastin synthesis in cultured fibroblasts derived from cardinal ligaments of patients with prolapsus uteri and compared them with those in fibroblasts from age-matched control patients were examined. Elastin mRNA steady-state levels and elastin synthesis were significantly down-regulated in quiescent fibroblasts from prolapsus uteri patients compared with quiescent control fibroblasts. Although transforming growth factor beta 1 (TGF-beta 1) promoted elastin mRNA and protein levels in fibroblasts from both prolapsus uteri and control patients, the maximum levels of elastin gene transcripts and elastin synthesis in response to exogenous TGF-beta 1 were significantly lower in prolapsus uteri fibroblasts than control fibroblasts. These results suggest that the marked reduction in elastin gene transcripts and elastin production in fibroblasts cultured from elderly women with prolapsus uteri could lead to a paucity of ligament elastic fibres and thus may contribute to the loss of supportive function in uterine connective tissues.

Cells, Cultured↗

PubMed1997

Cystic ganglioneurocytoma outside the ventricular region.

Recently cases of ganglioneurocytoma and cerebral neurocytoma, very rare variants of central neurocytoma, have been reported. The former is characterized by differentiation toward ganglion cells and the latter by extraventricular origin in the cerebrum, but their existence as distinct clinicopathological entities, is controversial. We report an unusual case of neurocytoma, which arose extraventricularly from the frontal lobe, formed a large cystic lesion and showed ganglioid differentiation, in a 11-year-old girl. Following subtotal tumor resection, she showed a satisfactory clinical course and no evidence of recurrence. This is a very rare case of central neurocytoma-like tumor outside the ventricular system and also of ganglioneurocytoma. This case may provide some insight into the tumorigenesis and widen the clinicopathological concept of neurocytoma.

Brain Neoplasms↗

PubMed1997

Smooth muscle cell proliferation, elastin formation, and tropoelastin transcripts during the development of intimal thickening in rabbit carotid arteries after endothelial denudation.

Extracellular matrix formation and smooth muscle cell proliferation are two major factors contributing to the development of intimal thickening after arterial injury. We investigated the elastin formation, tropoelastin transcripts, and proliferation of smooth muscle cells during the development of intimal thickening in rabbit carotid arteries after balloon endothelial denudation. Tropoelastin transcripts, identified by in situ hybridization using a digoxigenin-labeled probe, and elastin staining in the thickened intima were minimal 1 week after endothelial denudation when smooth muscle cell proliferation appeared throughout the thickened intima. A strong signal for tropoelastin transcripts was seen in the basal layer of the thickened intima 2 weeks after endothelial denudation, and then in the surface layer of the thickened intima 4 weeks after endothelial denudation. Immunohistochemistry for proliferating cell nuclear antigen and Ki-67, both markers for proliferating cell nuclei, showed that tropoelastin transcripts and elastin formation increased when smooth muscle cells enter quiescence after the end of the proliferative phase in the intima. Our findings strongly suggest that elastin synthesis and smooth muscle cell proliferation are tightly regulated during the repair of arterial wall injury.

Animals↗

PubMed1997

Changes in osteopontin mRNA expression during phenotypic transition of rabbit arterial smooth muscle cells.

Transition from a contractile to a synthetic phenotype appears to be an early key event during the development of intimal thickening after arterial wall injury. We examined the expression of osteopontin mRNA, proliferation, and phenotypic properties of smooth muscle cells (SMCs) in rabbit neointima after balloon denudation and in primary culture. A strong osteopontin mRNA signal was detected in the thickened intima 1 week after balloon denudation and in the surface layer of the intima 2 weeks after balloon denudation. Ki-67 immunohistochemistry showed that osteopontin mRNA expression increased when SMCs entered the proliferating phase in the intima. Rabbit arterial SMCs on type I collagen after 1 day of primary culture with growth factors, as well as freshly isolated cells, were in the G0 phase (contractile phenotype) and did not express osteopontin mRNA. After 3 days of culture, most cells entered the G1B phase (synthetic phenotype) and expressed osteopontin mRNA. In the absence of growth factors, most cells transferred to the G1A phase (intermediate phenotype) after 3 and 7 days, but did not express osteopontin mRNA. Our findings indicate that the osteopontin gene provides a marker that can be used to distinguish the phenotypic properties of vascular SMCs.

Animals↗

PubMed1997

Expression of p53 protein and p53 gene transcripts in rabbit carotid arteries after balloon denudation.

Smooth muscle cell (SMC) proliferation may be positively or negatively regulated by various factors after arterial wall injury. We investigated the hypothesis that the p53 protein may play a role in regulating SMC proliferation. We examined p53 protein expression and p53 gene transcript distribution in rabbit carotid arteries over a period of 6 weeks after balloon denudation in relation to SMC proliferation. The number of p53-positive SMCs in the neointima reached a maximum 2 weeks after balloon denudation when proliferating SMCs, decreased and were confined to the luminal surface of the intima. The p53-positive SMCs in the neointima almost paralleled the distribution of proliferating cell nuclear antigen (PCNA)-positive SMCs but not that of Ki-67-positive cells. Double immunofluorescence showed the simultaneous nuclear localization of both p53 protein and PCNA in intimal SMCs. Strong signals for p53 gene transcripts, identified by in situ hybridization, were observed in SMCs showing positive immunostaining for p53 protein. Our results indicate that p53 protein and p53 gene transcript levels increase, are closely linked to the proliferation of SMCs in the thickened intima, and play a key role in the regulation of cell proliferation during the repair process after arterial wall injury.

Animals↗

PubMed1997

Longitudinal MR imaging and proton MR spectroscopy in herpes simplex encephalitis.

Longitudinal MR imaging and proton MR spectroscopy were performed in an 11 year-old female case of herpes simplex encephalitis with a complete recovery. On MR imaging, the white matter lesions, which could be seen in the subacute stage, but not in the acute or chronic stage, might represent edema due to postinfectious neuroallergic phenomena. Proton MR spectroscopy revealed marked reduction of the NAA/Cr ratio in the chronic stage, which increased gradually to within normal range in a year.

Atrophy↗

PubMed1997

Comparison of moyamoya disease in Japan and moyamoya disease (or syndrome) in the People's Republic of China.

To find out the causes of many epidemiological differences in Moyamoya disease in Japan and in the People's Republic of China, we performed a bibliographical investigation and an actual survey and reached the following conclusions: (1) Leptospiral infection can cause Moyamoya syndrome which cannot be differentiated from Moyamoya disease unless confirmed through the patients past history and a positive serum test; and (2) Moyamoya disease reported in China may include Moyamoya syndrome caused by leptospiral or other cerebral arteritis.

Adolescent↗

PubMed1997

Development of intimal thickening in superficial temporal arteries in patients with moyamoya disease.

To investigate the possible mechanism of neointimal formation in Moyamoya disease, we histologically examined the superficial temporal arteries and also investigated cultured smooth muscle cells (SMCs) from the arteries. Intimal thickening of the scalp arteries developed significantly at an early age in Moyamoya patients compared with control subjects. The histopathological findings of the neointima in scalp arteries were almost similar to those in intracranial arteries in Moyamoya patients. SMCs cultured from Moyamoya arteries responded significantly less to serum mitogens, especially to platelet derived growth factor (PDGF), than those of control patients, the finding of which was explained by the reduced number of PDGF receptor on Moyamoya SMCs. Our findings indicate the presence of systemic factors that promote migration and proliferation of SMCs from the media to the intima in Moyamoya disease. Our results suggest that alteration in vascular cells may contribute to the development of intimal thickening in Moyamoya disease.

Adolescent↗

PubMed1997

Long-term intelligence outcome of post-encephalo-duro-arterio-synangiosis childhood moyamoya patients.

Long term post-encephalo-duro-arterio-synangiosis (EDAS) intelligence quotient (IQ) evaluated by Wechsler tests stays around the normal range (mean full intelligence quotient (FIQ), verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) at 100.0 +/- 155, 100.0 +/- 15.7 and 100.2 +/- 163, respectively) at more than 9.5 years after the operation, provided that the patient has FIQ above 70 pre-operatively. This fact encourages us to employ operative treatment for this difficult disease in which intelligence deterioration has been reported to be a common occurrence.

Cerebral Revascularization↗

PubMed1997

Parenchymal damage in the territory of the anterior choroidal artery following supraophthalmic intracarotid administration of CDDP for treatment of malignant gliomas.

We treated ten patients with malignant glioma by intracarotid chemotherapy with cis-diamminedichloroplatinum (CDDP) and/or 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-3-nitrosourea (ACNU). Three of the patients who underwent supraophthalmic intracarotid infusion of CDDP developed a low-density area in the basal ganglia on CT scan or an enhancing lesion in the hypothalamic region on MRI, with or without neurologic symptoms. No patient had such complications with supraophthalmic infusions of ACNU, or with cervical intracarotid infusion of CDDP or selective infusion of CDDP via the anterior or middle cerebral arteries. Supraophthalmic intracarotid administration of CDDP may augment drug delivery to tumors and prevent visual complications, but is accompanied by considerable risk of parenchymal damage in the territory of the anterior choroidal artery. Possible mechanisms for such complications are discussed.

Adult↗