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Biomedical subjects

Y Go

Publications and source records attributed to Y Go.

At least 19 recordsLinked to original sources

A case of papillary meningioma with a t(1;4)(q44;q21).

We report the results of cytogenetic analyses of three cases of meningiomas. The first case, a papillary meningioma, showed only one cytogenetic abnormality, 46,XX,t(1;4)(q44;q21). In contrast, the other two benign fibroblastic meningiomas showed loss of chromosome 22. Loss and/or rearrangement of chromosomes other than chromosome 22 appears to be associated with a more aggressive clinical course. It is suggested that a sole cytogenetic abnormality with a normal chromosome 22 indicates an atypical nature of meningioma.

Adult↗

PRINS analysis of the telomeric sequence in seven lemurs.

We examined the chromosomal localization of the telomeric sequence, (TTAGGG)n, in seven species of the lemurs and one greater galago, as an outgroup, using the primed in-situ labeling (PRINS) technique. As expected, the telomeric sequence was identified at both ends of all chromosomes of the eight prosimians. However, six species showed a signal at some pericentromeric regions involving constitutive heterochromatin as well. The pericentromeric region of chromosome 1 of Verreaux's sifaka (Propithecus verreauxi verreauxi) was labeled with a large and intense signal. The range of the signal considerably exceeded the area of DAPI positive heterochromatin. On the other hand, in the five lemurs, a large signal was detected also in the short arm of acrocentric chromosomes. Acquisition of the large block of the telomeric sequence into the acrocentric short arm might be interpretable in terms of the tandem growth of the heterochromatic short arm and the reciprocal translocation between heterochromatic short arms involving the telomeric sequence. Subsequently, it was postulated that meta- or submetacentric chromosomes possessing the telomeric sequence at the pericentromeric region could be formed by centric fusion between such acrocentric chromosomes.

Animals↗

Chromosomal localization of 18S rDNA and telomere sequence in the aye-aye, Daubentonia madagascariensis.

Chromosomal localization of 18S rDNA and telomere sequence was attempted on the chromosomes of the aye-aye (2n = 30) using fluorescence in situ hybridization (FISH) and primed in situ labeling (PRINS), respectively. The rDNA was localized at the tip or whole of the short arm of acrocentric chromosomes 13 and 14 in all spreads observed. However, post-FISH silver-nitrate (Ag) staining showed that transcriptional activity of the rRNA genes was variable, particularly in chromosome 14, which was most frequently negative in one homologue carrying the smaller copy number of rDNA. This observation supports, at the molecular cytogenetic level, previous data concerning the relationship between the copy number of rDNA and its trancriptional activity. On the other hand, telomere sequence was localized only at the telomeric region of all chromosomes, the so-called telomere-only pattern, a characteristic similar to that of the greater bushbaby. These data may provide information on the chromosomal evolution of the lemur, because locations of rDNA and telomere sequences frequently offer important clues in reconstruction of karyotype differentiation.

Animals↗

A novel role for the urokinase-type plasminogen activator receptor in apoptosis of malignant gliomas.

Glioblastomas express more urokinase-type plasminogen activator receptor (uPAR) than do low-grade gliomas and normal brain tissue. We previously showed that downregulation of uPAR through the transfection of SNB19 cells with an antisense cDNA construct corresponding to 300 bp of the 5' end of the human uPAR gene inhibited tumor cell invasion in vitro and tumor formation in vivo. Here we sought to determine whether uPAR is necessary for cell survival and whether the inhibition of tumor formation in nude mice is due to apoptosis of intracerebrally injected SNB19 cells. Apoptosis measured by DNA fragmentation were higher in the brains of animals injected with the antisense stable transfectants than in those injected with the parental cells. Moreover, the increase in apoptotic cell death in vitro was associated with increased expression of apoptotic protein BAX in antisense clones compared to controls. To our knowledge, this is the first report of uPAR playing a novel role in cell survival in human gliomas.

Animals↗

Brain abscess caused by Streptococcus intermedius: two case reports.

BACKGROUND: Although Streptococcus intermedius has been recognized as an important pathogen for abscess formation outside the central nervous System, the Streptococcus milleri group, of which it is a member, has not been recognized as a specific pathogen for brain abscess, often thought to be caused by Streptococcus viridans, which includes other streptococcal species. CASE DESCRIPTION: Two cases of brain abscess in the left frontal lobe caused by S. intermedius, which responded well to antimicrobial treatment combined with needle aspiration, are presented. In the first patient, the predisposing disease was paranasal sinusitis of the frontal and ethmoid sinuses. In the second patient, the source of the pathogen was not detected despite extensive examination. The patients underwent aspiration of pus under ultrasound guidance in the first patient, and via a computed tomography-guided stereotactic procedure in the second patient. They subsequently received appropriate antimicrobial therapy against S. intermedius isolated from the pus culture. Both patients were discharged without any neurological deficits. CONCLUSION: It is important to recognize S. intermedius as a pathogen of brain abscess, and to be aware of its predisposing factors, i.e., mucosal disturbance and liver abscess.

Adolescent↗

Experience with an ultrasonic aspirator in neuroendoscopy.

This report describes the clinical application of an ultrasonic aspirator for endoscopic neurosurgery. Eight patients with intraventricular hematoma with complete tamponade of the ventricular system and marked hydrocephalus were treated with the ultrasonic aspirator for endoscopic neurosurgery. Clinical evaluation and neuroimaging studies were obtained for one month. Removal of hematoma was confirmed on follow-up imaging. The ultrasonic aspirator is operated by electrostriction transducer on low generating power (15-30 watts). Its tube has an outer diameter of 1.8 mm. This aspirator is designed to fragment and aspirate the cattle-liver. On observing the adjacent neural and vascular structures with the neuroendoscope, the massive hematoma within the ventricles is removed with the use of this aspirator. Subtotal removal (> 90% of hematoma volume) was achieved in all patients. All patients tolerated the procedure well. However, postoperative re-rupture occurred in two patients prior to aneurysm clipping following an immediate interval. Three patients with hypertension, two patients with head trauma, and one patient after aneurysm clipping were discharged home within one month after treatment. Preliminary experience with this aspirator has demonstrated its feasibility and safety. Clinical application of this technique is expected in other fields of neurosurgery.

Adult↗

Neuroendoscopic approach to tectal tumors: a consecutive series.

OBJECT: The authors report a consecutive series of 10 patients who presented with signs and symptoms caused by tectal tumors. Clinical findings, radiographic features, neuroendoscopic management strategies, and histological findings are reported and discussed. METHODS: Since January 1990, 11 neuroendoscopic procedures were performed in 10 patients who harbored tectal tumors. The patients were followed for an average of 5 years (range 2 months-11 years), and a retrospective study was conducted in which case notes, radiological findings, operative notes, and histopathological findings were assessed. Magnetic resonance (MR) imaging was performed, and the images were used to classify patients into three groups: those with hypertrophy of the tectum in whom isointensity appeared on T1-weighted images (Group 1); those with a tectal tumor occupying the cerebral aqueduct in whom decreased signal intensity appeared on T1-weighted images, as well as no enhancement after gadolinium administration (Group 2); and those with a tectal tumor in whom mixed signal intensity and conspicuous evidence of contrast enhancement appeared on T1-weighted images (Group 3). The results of histological examination were consistent with MR imaging features: in Group 1, glial tissue or gliosis; in Group 2, benign astrocytoma; and in Group 3, malignant astrocytoma. Cerebrospinal fluid diversion was the only surgical treatment that provided relief from obstructive hydrocephalus. One patient in Group 3 underwent radiotherapy and subsequent partial tumor removal under neuroendoscopic guidance. Thereafter, the tumor remained in decline. All patients had normal intellectual status after undergoing surgery in which a neuroendoscope was used. CONCLUSIONS: Neuroendoscopic procedures can provide histological diagnosis, define the tumor-midbrain interrelationship, and be highly effective in treating obstructive hydrocephalus and in removing tectal tumors. This procedure may receive clinical application as a new management strategy for tectal glioma.

Adolescent↗

Elevated levels of urokinase-type plasminogen activator and its receptor during tumor growth in vivo.

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are important in the regulation of tumor tissue progenesis, cell differentiation, tumor cell motility, and tumor cell invasiveness. We have recently reported that the levels of uPA and uPAR were higher in malignant astrocytomas than in low-grade gliomas. In the present study, we measured the levels of uPA and uPAR during the growth of glioblastomas in nude mice. Using fibrin zymography, densitometry, and an enzyme-linked immunosorbent assay, we found that the enzyme activity and content of uPA were increased 4- to 10-fold during tumor formation. Using a receptor assay and an enzyme linked immunosorbent assay, we found the numbers and content of uPAR were increased 5- to 15-fold during tumor formation. In addition, immunohistochemical staining for uPA and uPAR revealed strong immunoreactivity in tumor cells with the staining more intense on day 28 than on day 14. These results suggest that the upregulation of uPA and uPAR plays a major role in the formation of gliomas.

Animals↗

Elevated levels of Mr 92,000 type IV collagenase during tumor growth in vivo.

Our previous studies demonstrated that matrix metalloproteinase (MMP-9) levels were significantly higher in human glioblastoma tissue samples than in low-grade brain tumors and normal brain tissue (Rao et al., Cancer Res. 53, 2208-2211, 1993). In the present study, we measured the levels of MMP-2 and MMP-9 during the growth of glial tumors in nude mice by intracerebral injection of glioblastoma cells. Using gelatin zymography, densitometry, and an enzyme-linked immunosorbent assay, we found that the enzyme activity and protein count of MMP-2 and MMP-9 were a respective 3- to 10- and 2- to 30-fold higher in tumors at day 14 and 28 than in normal tissue. Immunohistochemical staining for MMP-9 showed strong immunoreactivity in tumor cells and the staining intensity was much higher at day 28, compared to day 14. These results suggest that upregulation of MMP-9 plays a major role in the glioma tumor growth in vivo.

Animals↗

In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA receptor.

The cell surface urokinase-type plasminogen activator receptor (uPAR) has been shown to be a key molecule in regulating plasminogen-mediated extracellular proteolysis. To investigate the role of uPAR in invasion of brain tumors, human glioblastoma cell line SNB19 was stably transfected with a vector capable of expressing an antisense transcript complementary to the 300 base pair of the 5' end of the uPAR mRNA. Parental and stably transfected (vector, sense, and antisense) cell lines were analysed for uPAR mRNA transcript by Northern blot analysis, and receptor protein levels were measured by radioreceptor assays and Western blotting. Significant reduction of uPAR sites was observed in the antisense transfected cell lines. The levels of uPAR mRNA were significantly decreased in antisense clones compared to control, vector and sense clones. The invasive potential of the cell lines in vitro was measured by Matrigel invasion assay and migration of cells from spheroids to monolayers. The antisense transfected cells showed a markedly lower level of invasion and migration than the controls. The antisense clones were more adhesive to the ECM components compared to parental, vector and sense clones. All transfected (vector, sense and antisense) clones and parental cells produced similar levels of uPA activity without any significant difference however, MMP-2 activity was decreased in antisense clones compared to controls. These results demonstrate that uPAR expression is critical for the invasiveness of human gliomas and down regulation of uPAR expression may be a feasible approach to decrease invasiveness.

Blotting, Northern↗

Altered in vitro spreading and cytoskeletal organization in human glioma cells by downregulation of urokinase receptor.

The interaction of urokinase-type plasminogen activator (uPA) with its cell-surface receptor (uPAR) is implicated in diverse biological processes such as cell migration, tissue remodeling, and tumor cell invasion. Recent studies indicated that uPAR can act as an extracellular matrix receptor during cell adhesion. Recently, we showed that transfection of the human glioma cell line SNB19 with antisense uPAR resulted in downregulation of uPAR at both the mRNA and protein levels. In this study, we used SNB19 to determine how the presence or absence of uPAR promotes cell spreading and associated changes in cell morphology. Microscopic analysis of cell spreading revealed that antisense uPAR-transfected cells were larger, remained round, and did not spread efficiently over extracellular matrix substrate type IV collagen and fibronectin, unlike parental SNB19 cells, which were smaller and spindle shaped. Biochemical studies showed that antisense uPAR-transfected cells, in addition to not spreading, exhibited increased expression of alpha 3 beta 1 integrin but not alpha 5 beta 1 integrin. However, we could not find a change in the expression of extracellular matrix components or altered growth rate in these cells. Furthermore, despite the increased alpha 3 beta 1 integrin expression, antisense uPAR-transfected cells failed to form an organized actin cytoskeleton when plated on type IV collagen or fibronectin, unlike parental SNB19 cells, which displayed an organized cytoskeleton. These findings show that the absence of uPAR in human glioma cells leads to morphological changes associated with decreased spreading and a disorganized cytoskeleton resulting in altered cell morphology, suggesting that coordinated expression of uPAR and integrin may be involved in spreading of antisense uPAR-transfected glioma cells.

Cell Adhesion↗

Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors.

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5' end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.

Animals↗

Effect of cisplatin and BCNU on MMP-2 levels in human glioblastoma cell lines in vitro.

Matrix metalloproteinases (MMPs) play an important role in various physiological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to determine the effect of the antitumor compounds cis-dichlorodiammine platinum (ii) (cisplatin) and 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU) on 72-kDa type IV collagenase activity (MMP-2) in human gliomas. Human glioblastoma cell lines were treated with cisplatin (25 microM), and BCNU (50 microM), and the levels of MMP-2 were estimated in serum-free conditioned medium and in cell extracts at different time intervals. Gelatin zymography revealed increased levels of MMP-2 in serum-free conditioned medium and in cell extracts of untreated glioblastoma cell cultures during a 72-h period. In contrast, MMP-2 levels were significantly decreased in cisplatin-treated cells both in conditioned medium and cell extracts. However, no significant changes of MMP-2 levels were noted in BCNU-treated cells. Quantitative analysis of MMP-2 enzyme activity by densitometry and amount of MMP-2 protein by ELISA showed significantly decreased levels of MMP-2 in cisplatin-treated cells compared to BCNU and untreated glioblastoma cells. The results indicate that decreased levels of MMP-2 might represent an additional mechanism by which cisplatin provides its antineoplastic effects.

Antineoplastic Agents↗

Cisplatin but not BCNU inhibits urokinase-type plasminogen activator levels in human glioblastoma cell lines in vitro.

Glioblastomas extensively invade the surrounding normal brain tissue, with a concomitant expression of various proteolytic enzymes, in particular urokinase-type plasminogen activator (uPA). In this study we used cis-diamminedichloroplatinum (cisplatin) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), commonly used anti-cancer drugs for the treatment of glioblastomas, to study the expression of uPA in three human glioblastoma cell lines in vitro. Cells were treated with 25 microM cisplatin and 50 microM BCNU, and uPA levels were estimated by fibrin zymography during a 72-h time course. Treatment of glioblastoma cells with cisplatin resulted in significantly decreased levels of uPA in serum-free conditioned medium and cell extracts, compared to BCNU-treated and untreated cell lines. Quantitative levels of uPA enzyme activity assessed by scanning laser densitometry and uPA protein by ELISA using antibody against uPA showed decreased levels of uPA in cisplatin-treated glioma cell lines relative to BCNU and untreated cell lines. Our results suggest that anti-tumor compound, cisplatin, may exert its anti-neoplastic effects by inhibiting uPA in malignant glioblastomas.

Antineoplastic Agents↗

Invasive pattern of lac-Z-transfected human glioblastoma cells in nude mice brain.

Primary, malignant brain tumors show an extensive infiltrative invasion into surrounding normal brain. At present, little information is available regarding the local invasive behavior of human brain tumors and until now no animal model suitable to mimic human gliomas has been reported. To identify the infiltrative behavior of an established glioblastoma cell line (SNB19), we achieved a stable transfection of the SNB19 cell line with beta-galactosidase (lac-Z) plasmid. The stable beta-galactosidase-expressing cells were then injected intracerebrally into nude mice in an attempt to follow its pattern of spread. The mice were sacrificed at 3, 4, and 6 weeks postinjection. We could detect tumor formation in all of the animals, and the tumor size increased gradually over the 6 week time period. Three weeks after injection, tumor cells showed characteristic infiltrative invasion along the corpus callosum. We also observed tumor-cell invasion into the anterior commissure in some animals, and each tumor cell could be identified by lac-Z expression as visualized by its blue color. Further invasion was identified at 4 and 6 weeks postinjection. Our results suggest that this model could be used to study the molecular mechanisms involved in the invasion of gliomas so that appropriate therapeutic intervention strategies could be designed.

Animals↗

Expression of cathepsin D during the progression of human gliomas.

Recent studies suggest that aspartic proteinase cathepsin D may be implicated in tumor invasion and metastasis either directly by degrading extracellular matrix or indirectly by activating the cysteine proteinases such as procathepsin B, H, and L to mature forms or by inactivating cysteine proteinase inhibitors. In this study we determined for the first time whether increased levels of cathepsin D correlate with glioma progression by enzymatic assay, ELISA, and western blotting. Cathepsin D activity and content were higher in anaplastic astrocytoma and in glioblastoma tissue extracts especially when compared to normal brain tissue and low-grade gliomas. There was a significantly increased intensity of an M(r) 29,000 band in glioblastoma and anaplastic astrocytoma compared to low-grade glioma and normal brain tissue on Western blotting analysis using its specific antibodies. Cathepsin D antibody inhibited the invasion of glioblastoma cell lines in a dose-dependent manner. These results suggest that the expression of cathepsin D is dramatically upregulated in malignant gliomas, and that its increase correlates with the malignant progression of human gliomas in vivo.

Blotting, Western↗

Hemorrhage from abdominal non-Hodgkin's lymphoma treated successfully by emergency transcatheter arterial embolization.

A 49-year-old Japanese woman with follicular lymphoma who presented with severe abdominal and back pain is reported. She was known to have malignant lymphoma and had been previously treated with combination chemotherapy. An abdominal tumor occurring at the root of the mesentery and involving the superior mesenteric artery (SMA) had been diagnosed by computed tomography (CT), magnetic resonance imaging, and abdominal angiography. Emergent ultrasonography and CT findings showed intraperitoneal bleeding from the abdominal tumor. Selective SMA angiography revealed extravasation from a small branch originating from the dorsal pancreatic artery, which was embolized through a catheter by using platinum coils. It should be noted that a large tumor of malignant lymphoma, involving large vessels, may bleed, and in such a case selective transcatheter arterial embolization may be one of the effective modalities for hemostasis.

Abdominal Neoplasms↗

Role of extracellular matrix proteins in regulation of human glioma cell invasion in vitro.

Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasion. We examined the effect of type I and type IV collagens, fibronectin, laminin, and hyaluronic acid on the migration and invasion of four established glioblastoma cell lines, SNB19, U251, UWR1, and UWR2. Lower concentrations of all the ECM components induced the migration and invasion of all the cell lines. However, in the case of SNB19, laminin inhibited both migration and invasion in a concentration-dependent manner. We have also examined the influence of individual ECM components on the migration of cells from a spheroid to a monolayer on ECM component-coated coverslips. Consistent with the invasion studies using the modified Boyden chamber assays, lower concentrations of ECM components induced the migration of cells from spheroids to monolayer. Again, laminin inhibited the migration of cells from SNB19 spheroids. These results indicate that ECM components induce the invasion of glioma cells, apart from components like laminin, which may act as natural inhibitors.

Biological Assay↗