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Biomedical subjects

H Sawa

Publications and source records attributed to H Sawa.

At least 73 records · Page 4Linked to original sources
PubMed1999

[A case of primary cerebral neuroblastoma surviving for eight years].

We report a case of a patient with primary cerebral neuroblastoma who has survived for 8 years. A 10-year-old boy was admitted to our hospital because of headache and nausea. CT scan on admission revealed a large cystic tumor on the right frontal lobe. Subtotal tumor resection was carried out. A second operation was performed for the residual tumors which were removed meticulously with confirmation of the absence of tumor cells on each frozen section. After tumor removal, YAG laser was applied at each local area. Histological diagnosis disclosed primary cerebral neuroblastoma. Because of postsurgical meningitis and parent's refusal, neither chemotherapy nor radiation therapy was performed. There have been no findings of the tumor recurrence during the last eight years, and now the patient is enjoying high school life to the full, without any neurological deficits. In reviewing the literature, outcomes of neuroblastoma cases are very poor. Our case seems to be one of the rare long-survival cases.

Brain Neoplasms↗
PubMed1999

[Plasma D-dimer levels in patients with deep vein thrombosis].

Hemostatic abnormalities were examined in 40 patients with deep vein thrombosis (DVT), 40 patients treated with warfarin, and 30 healthy volunteers. Plasma D-dimer levels were measured by an enzyme linked fluorescent assay (ELFA; Vidas-D-dimer) and an enzyme immunosorbent assay (ELISA; D-dimer-ELISA). Plasma levels of D-dimer, thrombin-antithrombin complex (TAT), soluble fibrin monomer (SFM) were significantly higher in patients with DVT than in the other groups. Both the sensitivity and specificity of D-dimer for diagnosis of DVT were the highest among hemostatic molecular markers examined. The most adequate cut off value of Vidas-D-dimer was 0.6 microgram/ml. Plasma levels of Vidas-D-dimer were well correlated with D-dimer ELISA, SFM and TAT. As the time of measurement for Vidas-D-dimer is less than one hour, the measurement of D-dimer using a EFLA might be useful for the diagnosis of DVT in bed side.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.

Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The novel transcript shows no splicing at the downstream exon 4 boundary and encodes a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant; exon 5 is not included in the coding sequence which terminates downstream of exon 4. We here produced cells that exogenously express each form of cyclin D1 and analysed their cell cycle regulation. We found that (1) alternative splicing forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2) both splicing forms suppressed cell growth; and (3) cells overexpressing form [a] were inhibited from entry into and completion of the S phase, although form [b]-expressing cells showed no reduction of G1- to S transition. We also found that overexpression of either cyclin D1 form upregulated Rb gene products, suggesting that this upregulation may be one of the causes of growth suppression in cyclin D1 overexpressing cells.

Alternative Splicing↗
PubMed1998

Transforming growth factor beta2 in the vitreous in proliferative diabetic retinopathy.

OBJECTIVE: To evaluate the hypothesis that transforming growth factor beta2 (TGF-beta2) is involved in the cause of proliferative diabetic retinopathy (PDR). METHODS: We assayed TGF-beta2 levels in the vitreous of patients with PDR and other vitreoretinal disorders. Forty-nine vitreous specimens were obtained from eyes of patients with PDR undergoing vitrectomy, and 19 vitreous specimens from nondiabetic subjects served as controls. We assessed TGF-beta2 levels using an enzyme-linked immunosorbent assay. Both mature and total TGF-beta2 levels were quantified. RESULTS: The mean (+/- SD) total levels of TGF-beta2 were 2634 (+/- 1652) pg/mL in the patients with PDR and 1305 (+/- 972) pg/mL in controls. The mean (+/- SD) levels of mature TGF-beta2 were 244 (+/- 316) pg/mL in patients with PDR and 79 (+/- 81) pg/mL in controls. Total and mature TGF-beta2 levels were significantly greater in patients with PDR (total TGF-beta2, P <.001; mature TGF-beta2, P <.01). Mature TGF-beta2 levels were higher in the vitreous of patients who had severe fibrous proliferation. CONCLUSION: The results indicate increased levels of both total and mature TGF-beta2 in the vitreous of patients with PDR, suggesting that TGF-beta2 plays an important role in the pathogenesis of PDR.

Diabetic Retinopathy↗
PubMed1998

Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo.

Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of plasminogen activator inhibitor type 1 (PAI-1)in vivo. Others have demonstrated that increased PAI-1 activity is associated with coronary heart disease. Accordingly, the present study was performed to identify sites of increased expression of the PAI-1 gene within the vessel wall. Equimolar concentrations of insulin, proinsulin, or vehicle alone as a control, were administered intravenously over 1 h to conscious rabbits that were kept euglycemic throughout by the use of glucose clamping. Within 3 h plasma PAI-1 activity increased from 1.15+/-1.34 to 11.33+/-4.30 AU/ml with insulin (mean+/-s.d., P=0.015) and from 2.83+/-0.74 to 15.43+/-4.70 AU/ml with proinsulin (P=0.035). This was found to be in contrast to the controls where the increase in plasma PAI-1 activity was of lesser degree (2.43+/-1.86 to 6.80+/-1.10 AU/ml, P=n.s., n=4 each). As judged from the results of in situ hybridization, the site of prominent aortic expression of the PAI-1 gene was the endothelium. Furthermore, expression increased further in this site after administration of insulin or proinsulin. As judged from results of immunohistochemistry, PAI-1 protein in the aorta was also prominent in endothelium. These results suggest that "hyper(pro)insulinemia", increases PAI-1 not only in blood but also in arterial endothelium. Thus, attenuation of vasculopathy and especially of restenosis after angioplasty in type II diabetes may be possible with somatic gene therapy targeting PAI-1 expression in endothelial cells.

Animals↗
PubMed1998

Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6).

SCA6 is an autosomal dominant spinocerebellar ataxia (SCA) caused by a small CAG repeat expansion of the gene encoding an alpha-1A-voltage-dependent Ca channel gene subunit on chromosome 19p13. A Japanese woman with SCA6, with a 7-year history of progressive pure cerebellar ataxia, died of malignant lymphoma. Systematic neuropathological examination showed that neuronal degeneration was confined to the cerebellar Purkinje cells and, to a lesser degree, the granular cells, without any involvement of other central nervous system structures. Such pathological selectivity correlates with the localized expression of the responsible gene, and coincides with the neurological manifestation. These findings might contribute to establishing the phenotype of the SCA6 via comparison with other dominant ataxias.

Age of Onset↗
PubMed1998

Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas.

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4-8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.

Adult↗
PubMed1998

Delayed cyst formation after radiosurgery for cerebral arteriovenous malformation: two case reports.

Two patients who underwent gamma knife radiosurgery for ruptured cerebral arteriovenous malformations (AVM) developed cystic lesions at 78 and 111 months after undergoing treatment. Both patients presented initially with intracerebral hemorrhage. In one patient, the cystic lesion was discovered during routine follow-up imaging and clinical examination revealed homonymous hemianopsia; the second patient presented with seizure and the lesion was identified more than 9 years after radiosurgery. One patient underwent resection of the nidus and histologic analysis of the resected specimen showed vessels in various stages of obliteration. The present paper discusses the possible mechanism for the delayed development of cystic lesions, and the possibility that radiation-induced vascular changes may continue in a nidus even when angiography shows complete obliteration of the nidus.

Adult↗
PubMed1998

Spreading depression induces depletion of MAP2 in area CA3 of the hippocampus in a rat unilateral carotid artery occlusion model.

Traumatic brain injury (TBI) induces neuronal cell loss in area CA3 of the hippocampus. However, it has not yet been established why traumatic injury of the cortex induces neuronal damage in more remote areas. Spreading depression (SD) may be one potential mechanism for this pathophysiology. The present study evaluated whether SD on the cortex evokes a pathological change in the hippocampus. Forty-two Fisher rats were assigned to four groups: Group I: sham operation (n = 7), Group II: right carotid occlusion (UO) for 7 days (n = 7), Group III: repeated induction of SD by KCl application on dura for 7 days (n = 7), Group III' for 3 h (n = 7), Group IV: SD induction and UO for 7 days (n = 14) Group IV' for 3 h (n = 7). In 5 out of 7 animals in Groups III' and IV', cerebral blood flow (CBF) was monitored using laser Doppler flowmetry for 3 h during the passage of SD. The brains were processed for immunohistochemical analysis of microtubule-associated protein 2 (MAP2). Reactive hyperemia induced by SD was not significantly suppressed by right carotid occlusion (194 +/- 25% and 181 +/- 42% UO in Groups III and IV, respectively). In 6 out of 7 animals in a 7-day model of Group IV, and 3 animals in a 7-day model of Group III, MAP2 depletion in the CA3 area of the hippocampus (partly including CA2) was observed, although no change in the hippocampus was observed in other groups. In conclusion, SD in combination with UO yielded reproducible lesions in CA3. Neuronal injury in the hippocampus after brain trauma may be attributable to SD in combination with the blood flow restriction.

Animals↗
PubMed1998

Functional role of focal adhesion kinase in the process of implantation.

The expression and function of focal adhesion kinase (FAK) in human decidual cells were investigated. This kinase is localized to focal adhesions in fibroblasts, and is phosphorylated on tyrosine in normal and src-transformed fibroblasts. Immunofluorescent staining revealed that the cultured decidual cells expressed high levels of FAK at the cell periphery. Double stainings for FAK and phosphotyrosine, FAK and talin, and FAK and beta1 integrin demonstrated that FAK co-localized with integrins in cellular focal adhesions. Mouse blastocysts became attached to cultured decidual cells after embryos hatched from the zona pellucida. The majority of hatched blastocysts attached to human decidual cells within 24 h of culture. Blastocysts attached to decidual cells exhibited extensive outgrowth after 48 h. Treatment of decidual cells with herbimycin A, a tyrosine kinase inhibitor, did not affect the rate of hatching or attachment of blastocysts. However, the outgrowth of embryos on the decidual cells was inhibited by the addition of herbimycin A in a dose-dependent manner, implying that blastocyst attachment and outgrowth are mediated by different mechanisms. This study suggests that tyrosine phosphorylation of FAK on decidual cells may be important in development and differentiation following attachment.

Adult↗
PubMed1998

Vitrectomy for proliferative diabetic retinopathy with asteroid hyalosis.

PURPOSE: To characterize the clinical features of proliferative diabetic retinopathy (PDR) with asteroid hyalosis treated by pars plana vitrectomy. METHODS: Vitrectomy was performed in 26 eyes with PDR accompanied by asteroid hyalosis (7 eyes with vitreous hemorrhage, 6 eyes with tractional retinal detachment with vitreous hemorrhage, and 13 eyes with tractional retinal detachment without vitreous hemorrhage). We observed the occurrence of posterior vitreous detachment intraoperatively and evaluated the clinical characteristics retrospectively. RESULTS: In 24 eyes, posterior vitreous detachment was slight, necessitating artificial detachment. Of the 26 eyes, 20 experienced iatrogenic retinal breaks and 6 (23%) experienced postoperative retinal detachment due to iatrogenic breaks. Three cases worsened to anterior proliferative vitreoretinopathy and retinal reattachment could not be achieved. CONCLUSIONS: In vitrectomy for PDR with asteroid hyalosis, and in cases of simple vitreous hemorrhage, surgery should be performed with full understanding of the anatomic characteristics. Notably, if posterior vitreous detachment is not present, the occurrence of iatrogenic retinal breaks is more likely.

Adult↗
PubMed1998

Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: analyses of 84 soft tissue and bone tumors.

The chimeric transcript SYT-SSX is generated as a result of reciprocal translocation t(X;18), which is the primary cytogenetic abnormality found in, and appears to be specific for, synovial sarcoma. We performed a reverse transcriptase-polymerase chain reaction (RT-PCR) for SYT-SSX transcripts in a series of 84 tumors (61 soft tissue tumors and 23 bone tumors), including a variety of histologic types, to assess its usefulness in molecular diagnosis. Ten synovial sarcomas, three tumors initially unclassified, and one malignant peripheral nerve sheath tumor contained the chimeric transcripts. A review of the original slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. Additionally, in situ hybridization with an SSX1 probe indicated that the chimeric transcripts exist not only in the cells of special components but also in cells showing a variety of histologic patterns. Therefore, RT-PCR can be considered a useful molecular biological technique that can provide objective evidence for diagnosis of synovial sarcoma. Northern blot analysis with an SSX1 probe also detected chimeric SYT-SSX transcripts in the synovial sarcoma cases. The additional smaller bands, however, were also detected in six peripheral primitive neuroectodermal tumors (pPNETs) and one embryonal rhabdomyosarcoma. In five of these pPNETs, other bands ranging in size from 2.0 to 2.2 kb were also found, and it seems possible that these bands might represent novel karyotypic aberrations and/or splicing variants of SSX.

Adult↗
PubMed1998

[Neovascularization from the scleral wound as the cause of vitreous rebleeding after vitrectomy for proliferative diabetic retinopathy].

Vitreous hemorrhage recurred in 11 eyes out of a series of 120 eyes treated by vitrectomy for proliferative diabetic retinopathy during a 10-month period. Neovascularization from the scleral wound, or fibrovascular proliferation, was identified as the cause of rebleeding in 4 eyes from findings during revitrectomy. None of the 4 eyes showed retinal disorders attributable as the cause of rebleeding. Rebleeding in these 4 eyes developed after an average of 9.0 weeks after initial surgery. The proliferative membrane was oval in shape and expanded from the residual vitreous which had been incarcerated in the scleral wound. The proliferative membrane obtained during revitrectomy was poor in cellular components and contained extracellular matrix. Blood vessels of various sizes were also present. Electron microscopically, the membrane was rich in extracellular components. It contained two types of cells, i.e., high and low electron density cells. These cells often had microvilli and seemed to be of epithelial origin. The findings show that vitreous rebleeding may develop from fibrovascular proliferation from the scleral wound after diabetic vitrectomy. The proliferated membrane showed histological similarities with the fibrovascular proliferation usually seen in the diabetic retina and may represent a type of anterior proliferation secondary to retinal ischemia.

Aged↗
PubMed1997

Advanced glycation end products induce expression of vascular endothelial growth factor by retinal Muller cells.

Recent studies have suggested that advanced glycation end products (AGEs) are involved in the development of diabetic complications. To assess the pathogenic role of AGEs and vascular endothelial growth factor (VEGF) in the development of retinal neovascularization in diabetic retinopathy, we investigated the effect of AGEs on induction of VEGF by retinal Muller cells and measured AGE and VEGF concentrations in the vitreous of patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the production of VEGF protein by cultured Muller cells were enhanced by the presence of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in patients with PDR compared with patients without diabetes (P < 0.01). There was a moderate positive correlation between the levels of crossline and VEGF (r=0.698, P < 0.01). Elevation of AGEs in the vitreous may promote intraocular neovascularization in diabetic retinopathy through production of VEGF from Muller cells.

Aged↗
PubMed1997

Overexpressed syntaxin 1A/HPC-1 inhibits insulin secretion via a regulated pathway, but does not influence glucose metabolism and intracellular Ca2+ in insulinoma cell line beta TC3 cells.

We have previously established a stable beta TC3 cell line that overexpresses syntaxin 1A, designated beta TC-hpc1 cells, in which glucose-stimulated insulin release was decreased. Using beta TC-hpc1 cells, we aimed to determine whether syntaxin 1A functions in the regulatory or constitutive pathway of insulin release. We therefore examined the secretion of phorbol-12-myristate-13-acetate (TPA)-stimulated newly synthesized proinsulin/insulin and total immunoreactive insulin. beta TC3 and beta TC-hpc1 cells were simultaneously pulse-labeled with 3H-leucine for 30 min in 11 mM glucose and chased for 1 h in one of a number of different concentrations of TPA in 11 mM glucose. Total immunoreactive insulin release (IRI) by both cell types during the chase period was markedly increased by the addition of TPA in a dose-dependent manner; however, the IRI from beta TC-hpc1 cells was lower than that from beta TC3 cells. The secretion of newly synthesized proinsulin/insulin from both cell types, which in beta TC3 cells is thought to occur via a constitutive pathway, was in the same range under any condition. Thus, the evidence indicates that syntaxin 1A preferentially functions in the regulated insulin release pathway in beta TC3 cells. In order to clarify the effect of overexpressed syntaxin 1A on glucose metabolism and intracellular Ca2+ we analyzed the glucose transport system, glucose phosphorylation activity, and cytosolic concentration of free Ca2+ ([Ca2+]i). 2-Deoxy-glucose uptake and the content of GLUT1 protein in the plasma membrane fractions of beta TC-hpc1 cells were not different from those of beta TC3 cells. Radiometric assays of glucose phosphorylation activity showed that there were no differences in hexokinase activity and glucokinase activity between beta TC3 and beta TC-hpc1 cells. [Ca2+]i measured by using fura 2 demonstrated that there was no difference in [Ca2+]i between beta TC3 and beta TC-hpc 1 cells under glucose-stimulated conditions. The present experiments indicate that syntaxin 1A plays a central role in a late step of the regulatory insulin release pathway without a change in glucose metabolism and [Ca2+]i in beta TC3 cells.

Animals↗
PubMed1997

Experimental studies of stereotactic laser balloon hyperthermic treatment.

BACKGROUND AND OBJECTIVE: The hyperthermic treatment of small malignant brain tumors in basal ganglia and other eloquent cortical areas was investigated with a stereotactic Nd:YAG laser balloon unit. STUDY DESIGN/MATERIALS AND METHODS: An Ultra Line fiber (Heraeus Laser Sonics, CA) was inserted into a 6 F silicone balloon catheter, which caused the laser beam to be directed 80 degrees laterally. The balloon was inflated with physiologic saline to make the tumor tissue surrounding the laser fiber hypoxic. The hypoxia enhances the thermal effect on the tumor. The laser power was set at 5 watts (W) and a computer, programmed with specific parameters using feedback control was used to maintain the tissue 10 mm distant from the laser fiber at a temperature of 45 degrees C. Forty five minutes of hyperthermic treatment was applied to an implanted subcutaneous glioma in a rat. RESULTS/CONCLUSION: The thermally induced damaged in the tumor appeared as a fan-shape lesion extending at a 100 degrees angle from the laser beam axis. The entire tumor could be treated by rotating the laser fiber in the balloon catheter.

Animals↗