Biomedical subjects

T Ohmoto

Publications and source records attributed to T Ohmoto.

At least 73 records · Page 4Linked to original sources

PubMed1999

[A clinical analysis of patients with primary intracranial germinomas: the relationship between proliferative potential and recurrence].

We analyzed clinically 30 germinomas (22 pure germinomas and 8 germinomas with syncytiotrophoblastic giant cell (STGC) and also investigated the proliferative potential of 18 germinomas immunohistochemically using MIB-1 monoclonal antibody in formalin-fixed paraffin-embedded sections. The majority of patients responded favorably and completely to the treatment. Seven patients (four had germinomas with STGC and the other three had pure germinomas) suffered recurrence after a complete response to radiotherapy and/or chemotherapy. The patients with germinomas with STGC experienced recurrence significantly more often than those with pure germinomas (P < 0.01). Three of the patients died. The MIB-1 indexes of the germinomas ranged from 18% to 80%. The average MIB-1 index of pure germinomas is 58.5 +/- 17.3%, that of germinomas with STGC is 45.3 +/- 17.1%. There was no significant difference between the two groups. The MIB-1 indexes of 3 recurrent cases were 64.3%, 51.9%, and 20.8%, respectively. There were no significant differences in the MIB-1 indexes between nonrecurrent cases and recurrent ones.

Adolescent↗

PubMed1999

[Clinical results of supratentorial astrocytoma grade II].

At present, there is no consensus concerning the treatment of low-grade gliomas. The authors conducted a retrospective review of surgically treated, histologically verified cases of supratentorial astrocytomas of grade II to evaluate the results of current treatment methods. Thirty-seven patients, 23 males and 14 females, treated from April, 1977 through March, 1997 were analyzed. Median patient age was 36 years (range 2-69 years). All patients were diagnosed by surgical specimens. Thirty were fibrillary, and three were gemistocytic astrocytomas. There were 13 total resections, 7 subtotal resections, 10 partial resections. Of the remaining 7, diagnosis was obtained by stereotactic biopsy. Twenty patients were irradiated and two received chemotherapy. Follow-up information was obtained for 33 patients. The follow-up time ranged from 4 months to 246 months (mean, 9 years). Overall survival rates at 5 and 10 years for the entire treated group were 71% and 57% respectively. Total and subtotal resections were significantly associated with longer survival time, the 5- and 10-year survival rates were 93% and 67%, respectively. They were 40% and 40% in patients with partial resection or needle biopsy. Patients with gemistocytic astrocytoma had a poor prognosis with a median survival of 44.5 months. The influence of radiotherapy was not obvious: 92 and 69% of patients were alive at 5 and 10 years respectively without radiotherapy. The extent of surgery and histological type were by far the most important factors in predicting length of survival. The importance of an accurate histologic diagnosis and a gross total resection is emphasized.

Adolescent↗

PubMed1999

Expression of cell cycle regulator p27Kip1 is correlated with survival of patients with astrocytoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 for astrocytomas. Tissue samples from 130 astrocytomas (WHO grade 1, 5 cases; grade 2, 23 cases; grade 3, 64 cases; grade 4, 38 cases), including 92 primary and 38 recurrent tumors, were examined immunohistochemically for Ki-67 and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The p27Kip1 labeling index (LI) ranged from 2.3 to 98.4%, with a mean value of 47.5% (+/-23.4%). The p27Kip1 LI decreased with increasing tumor grade but did not correlate with other parameters. There was no correlation between Ki-67 LI and p27Kip1 LI. For patients with primary astrocytomas, the 50% survival times of those with low p27Kip1 LI (<50%) and those with high p27Kip1 LI (> or =50%) were 17.1 and 69.6 months, respectively. For patients with high-grade tumors, the 50% survival times were 13.1 months for those with low p27Kip1 LI and 33.7 months for those with high LI. On multivariate analysis, p27Kip1 was one of the most significant prognostic factors, indicating that low p27Kip1 LI was associated with poor prognosis (primary, risk ratio = 2.5, P = 0.0023; high-grade, risk ratio = 2.2; P = 0.0139). The expression of p27Kip1 was inversely related to tumor grade and positively related to favorable outcome of patients with astrocytoma, suggesting that p27Kip1 may be a candidate for prognostic factor for this tumor.

Adolescent↗

PubMed1999

[Analysis of spinal cord hemangioblastoma in von Hippel-Lindau disease].

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder showing various clinical features. We analyzed 6 patients with spinal cord hemangioblastoma associated with VHL disease in four families. All patients had cerebellar hemangioblastomas. Four cases carried retinal hemangioblastoma and 5 cases showed visceral lesions; renal cell carcinoma (2 cases), renal cyst (2 cases), pancreas cyst (2 cases) and paraovarian tumor. In four cases, spinal cord hemangioblastomas were multiple. Ten symptomatic or rapidly growing lesions in 5 patients were surgically resected. Two of these lesions were extramedullary spinal root hemangioblastoma. Operative results were good except for a case of ventrally placed thoracic spinal intramedullary hemangioblastoma who showed paraparesis postoperatively. One patient who suffered from complete paraplegia preoperatively did not recover after surgery. In two patients, renal cell carcinoma was detected and nephrectomy was undergone. It was noteworthy that metastasis of renal cell carcinoma to the hemangioblastoma was histologically proved with anti-cytokeratin immunostaining in two patients with VHL-associated renal cell carcinoma. Molecular genetic analysis showed a missence mutation in one family and possible intragenic deletion in another family. However, two families showed no VHL gene mutation with single strand conformational polymorphism or Southern blot analyses. Spinal cord hemangioblastomas in VHL disease are often multiple and located at various sites and seem to be underestimated. Surveillance should start in childhood and requires annual follow-up with imaging of the central nervous system and abdominal viscera. Presymptomatic diagnosis by gene analysis can be very useful for early detection of this disease.

Adolescent↗

PubMed1999

[Combination effect of hyperthermia and MX2 on cultured glioma cell lines].

MX2, a new lipophilic morpholino anthracycline, has been reported to have chemotherapeutic effects superior to those of adriamycin against murine and human glioma cells in vitro and in vivo. To assess the combination effect of MX2 and hyperthermia in vitro, the thermo-chemosensitivities of cultured human (U251MG and KC) and rat (C6 and 9L) glioma cell lines were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The number of viable cells in each cell line was markedly and dose-dependently decreased by MX2 treatment, but the sensitivity of U251MG to MX2 was less than that of the other cell lines. The survival of each cell line was decreased with the hyperthermic treatment at 43 degrees C for 60 minutes. Combined treatment with MX2 and hyperthermia had an additive effect on cultured glioma cells when MX2 was added to the medium at a dose below 50 ng/ml. However, combined treatment indicated neither an additive nor a synergistic effect when the dose of MX2 was above 50 ng/ml. We conclude that MX2 may be clinically useful against malignant gliomas when administered alone or in combination with hyperthermia.

Animals↗

PubMed1998

GDNF administration induces recovery of the nigrostriatal dopaminergic system both in young and aged parkinsonian mice.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopaminergic system. GDNF was injected stereotaxically into the striatum of young (2 months old) and aged (12 months old) C57BL/6 mice that were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. Immunocytochemical and neurochemical analyses showed significant recovery of the nigrostriatal dopaminergic system both in young and in aged mice. Since Parkinson's disease is a neurodegenerative disorder mainly affecting elderly people, this result demonstrates the potential usefulness of GDNF in treating Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Decoy administration of NF-kappaB into the subarachnoid space for cerebral angiopathy.

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.

Animals↗

PubMed1998

Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex.

As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of Parkinson's disease (PD) in the present study. Following continuous injection for 7 days, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by a bovine papilloma virus-based plasmid vector were efficiently introduced into glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant recovery in apomorphine-induced rotational behavior of PD models was obtained by transfection of TH gene and this effect continued for up to 5 weeks after injection. Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone. We suggest that this approach is a controllable and manageable alternative to other methods of gene therapy for the treatment of PD.

Animals↗

PubMed1998

In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex.

Previously reported methods of liposome-mediated direct in vivo gene transfer have been inefficient, especially when performed with highly differentiated, quiescent cells of the adult mammalian central nervous system (CNS). We have therefore improved these procedures based upon a novel concept. Following continuous injection of plasmid DNA-cationic liposome complex which contained a reporter gene encoding E. coli beta-galactosidase into the striatum of adult rats, the expression of transgene was dramatically elevated without any adverse effects. This new technique may enable a wide application of liposome-mediated gene transfer technology not only to basic analysis of gene functions in the brain but also for clinical treatment of certain CNS disorders.

Animals↗

PubMed1998

Effects of lecithinized SOD on sequential change in SOD activity after cerebral contusion in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.

Animals↗

PubMed1998

"Kissing" bilateral large carotid-ophthalmic aneurysms. A case report.

A case of unruptured bilateral large carotid-ophthalmic aneurysms, which appear to be adjoining and "kissing" each other when visualized by three-dimensional computed tomographic angiography (3-D CTA), is reported. Although bilateral carotid-ophthalmic aneurysms are not rare, bilateral large ones are quite rare, and direct imaging of "kissing aneurysms" of this portion has not been reported. Since 3-D CTA is becoming a useful tool for the diagnosis of cerebral aneurysms, we propose that these and similar bilateral large carotid-ophthalmic aneurysms are good candidates for the term "kissing aneurysms".

Aged↗

PubMed1998

Primary brain tumors in children under age 3 years.

During the period from 1966 to 1996 the authors analyzed the clinicopathological characteristics of 46 cases of histologically verified primary brain tumors with symptomatic onset during the first 3 years of life. The patient group included 27 males and 19 females. There were 14 patients during the first year, 13 during the second year, and 19 during the third year. Supratentorial tumors (60.9%) were more common than infratentorial tumors. Histologically, neuroepithelial tumors predominated. The incidence of ependymal tumors, particularly malignant ones, and of neuronal/mixed neuronal-glial tumors was higher than in previous reports. Congenital brain tumors, those occurring within 2 months after birth, or tumors of dysplastic origin comprised 42.9% of the tumors that developed within 1 year of birth. At the onset, macrocephaly, failure to thrive, and seizures were prominent symptoms or signs in the younger patients. Focal neurological deficits and increased intracranial pressure predominated in the older patients. All but one patient underwent surgical treatment, and 17 patients received adjuvant therapy after surgery. The prognosis was mainly related to the histology of the malignancy. The outcome of medulloblastomas was poor. The quality of life of surviving patients was relatively good, 77.8% having better performance status (PS) than the Eastern Cooperative Oncology Group PS 2.

Brain Neoplasms↗

PubMed1998

Malignant cerebellar astrocytoma developing 15 years after radiation therapy for a medulloblastoma.

A case of malignant cerebellar astrocytoma occurring 15 years after the radiation therapy for a medulloblastoma is reported. The tumor developed at the same site of irradiation after a sufficient latent period and was completely different from medulloblastoma in its histology. This tumor fulfilled the criteria of radiation-induced neoplasm. Only seven similar cases have been reported up to the present. Whole neuraxis irradiation following a gross total resection is a standard treatment for medulloblastoma, but the possibility of the development of radiation-induced tumors must be borne in mind for a long time after the radiation therapy for medulloblastoma.

Adult↗

PubMed1998

Cerebral aneurysms causing visual symptoms: their features and surgical outcome.

Cerebral aneurysms causing visual symptoms before surgery are relatively rare. We have experience with 17 cases of such aneurysms and report their clinical features and surgical outcome. The locations of aneurysms presenting with visual dysfunction in our series are as follows: internal carotid (IC)-cavernous aneurysms in six of 29 total cases, 21%; IC-ophthalmic aneurysms in nine of 36 total cases, 25%; and anterior communicating artery (A com A) aneurysms in two of 217 total cases, 1%. The size of the aneurysms, the period between the onset of symptoms and surgical treatment, the pre- and post-operative visual function, and the surgical methods used to treat the aneurysm were analyzed. All the visually symptomatic cases featured large (15-24 mm) or giant (> 25 mm) aneurysms. Visual symptoms occurred before aneurysmal rupture in all cases but one. The type of visual field defect and the degree of reduced visual acuity were highly variable, without a typical clinical presentation. Five out of six IC-cavernous aneurysms were treated surgically with common carotid artery (CC) ligation or IC ligation with superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis. Three of these cases showed improvement of visual symptoms after surgery. Six out of nine IC-ophthalmic aneurysms were treated surgically (CC ligation or direct clipping), with four cases showing improvement of visual symptoms after surgery. One case of an A com A aneurysm featured a ruptured aneurysm that had physically penetrated the optic chiasm, while the other case was a giant unruptured aneurysm. The interval between the onset of symptoms and surgical treatment was the only factor identified which affected the clinical outcome of the aneurysms presenting with visual dysfunction. All cases that were determined to show improvement of visual function were treated surgically within 3 months of the onset of symptoms. Cerebral aneurysms presenting with visual dysfunction before surgery are most commonly large or giant, and unruptured. Recovery of visual function can most often be expected when surgical treatment is performed expeditiously, before the visual dysfunction becomes irreversible.

Adult↗

PubMed1998

Primary intracranial germinoma involving the midbrain.

To our knowledge, this is the first reported case of a germinoma involving the midbrain without the demonstrable coexistence of any common midline tumors. A 27-year-old man was referred to our institution for evaluation and treatment of diplopia persisting for 5 years. Magnetic resonance imaging (MRI) showed the mass in the midbrain to be of iso intensity on T1-weighted images, and of high intensity on T2-weighted images with homogeneous enhancement. MRI-guided stereotactic biopsy was performed, and the histologic diagnosis was germinoma. Following biopsy, external beam radiotherapy of 50 Gy (whole brain 30 Gy: local 20 Gy) was performed. At the time of discharge, the patient's neurological symptoms had resolved. Follow-up MRI revealed disappearance of the tumor. These findings suggest the diagnostic value of magnetic resonance image-guided stereotactic biopsy in the differential diagnosis of adult brainstem lesions, which should now include germinoma.

Adult↗

PubMed1998

Picrodendrin and related terpenoid antagonists reveal structural differences between ionotropic GABA receptors of mammals and insects.

Twenty-eight picrotoxane terpenoids, including picrodendrins isolated from the Euphorbiaceae plant, Picrodendron baccatum (L.) Krug and Urban, have been evaluated for their ability to inhibit the specific binding of [3H]EBOB, the noncompetitive antagonist of ionotropic GABA receptors, to rat-brain and housefly (Musca domestica L.)-head membranes. Picrodendrin Q was the most potent competitive inhibitor of [3H]EBOB binding, with IC50 values of 16 nM (rat) and 22 nM (Musca). We find that the spiro gamma-butyrolactone moiety at the 13-position, which contains a carbonyl group conjugated with an unsaturated bond, and the substituents at the 4-position play important roles in the interaction of picrodendrins with their binding site in rat receptors. In contrast, such structural features are not strictly required in the case of the interaction with Musca receptors; the spiro saturated gamma-butyrolactone moiety at the 13-position, which bears the 16-sp3 carbon atom, and the hydroxyl groups at various positions are somewhat tolerated. Quantitative structure-activity studies have clearly shown that the electronegativity of the 16-carbon atom and the presence or absence of the 4- and 8-hydroxyl groups are important determinants of the potency of nor-diterpenes in Musca receptors, while the negative charge on the 17-carbonyl oxygen atom is likely important in the case of rat receptors. These findings indicate that there are significant differences between the structures of the complementary binding sites in rat GABA receptors and Musca GABA receptors. We also infer differences between native Musca GABA receptors and the Drosophila Rdl subunit-containing homo-oligomeric GABA receptors in the structures of their binding sites.

Animals↗

PubMed1998

Tips for preventing cerebrospinal fluid rhinorrhea after acoustic neurinoma surgery: technical note.

CSF rhinorrhea is a common complication of acoustic neurinoma surgery via the suboccipital route. In this paper we present our incidence of CSF rhinorrhea and our surgical techniques for reducing the risk of this post-surgical complication. Following removal of the acoustic neurinoma, the drilled posterior wall of the internal auditory canal is covered with bonewax, muscle or fat pieces, and fibrin-glue, while the previously reflected dura is sutured in place keeping the packing material in position. Bone chips removed during the craniectomy are then mixed with fibric glue and are used for a cranioplasty. Although we routinely perform aggressive drilling of internal auditory canal to facilitate total removal of the acoustic neurinoma, only 1 out of 94 consecutive cases (1%) showed postoperative CSF rhinorrhea. Since previous reports mention the rate of this complication following acoustic neurinoma surgery varies between 4% and 27%, we believe that our methods may be useful in helping reduce the incidence of postoperative rhinorrhea.

Journal Article↗

PubMed1998

Purification and some properties of 2-hydroxychromene-2-carboxylate isomerase from naphthalenesulfonate-assimilating Pseudomonas sp. TA-2.

A 2-hydroxychromene-2-carboxylate isomerase was purified from a cell-free extract of naphthalenesulfonate-assimilating Pseudomonas sp. TA-2 to an electrophoretically homogeneous state by successive column chromatography on DEAE-cellulose, DEAE-Toyopearl 650M, Sephadex G-75, Hydroxyapatite, and Mono Q. The enzyme had a molecular mass of 25 and 27 kDa as estimated by SDS-PAGE and Superdex 200, respectively. Its N-terminal 30 amino acid sequence had high homology with the deduced amino acid sequences of the 2HC2CA isomerase of nahD (a gene of naphthalene metabolism), pahD (a gene of naphthalene and phenanthrene metabolism), and doxJ (a gene of dibenzothiophene metabolism). The enzymatic product was a trans isomer. The isomerase activity was inhibited in the presence of monoiodoacetate or Hg2+, but not by preincubation with monoiodoacetate or N-ethylmaleimide. GSH functioned as a cofactor and activated the enzyme at above 0.15 mM.

Amino Acid Sequence↗