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Biomedical subjects

T Ohmoto

Publications and source records attributed to T Ohmoto.

At least 91 records · Page 5Linked to original sources

Partial thrombosis of canine carotid bifurcation aneurysms with cellulose acetate polymer.

OBJECTIVE: To investigate the usefulness of a cellulose acetate polymer (CAP) solution for partial thrombosis of aneurysms. METHODS: We created 14 canine cervical carotid bifurcation aneurysms, 11 of which were subsequently thrombosed partially with CAP solution. We then conducted angiographic and histological investigations. RESULTS: Nine aneurysms were thrombosed 50 to 70% by volume, although a significant crescent crevice between the aneurysmal sac and the CAP mass was left in four of the aneurysms. In the remaining two aneurysms in which a crescent crevice had been seen in the initial stage of CAP injection, 80% and more than 95% thrombosis were needed to occlude the crevice, respectively. Follow-up angiograms of the seven aneurysms with no crescent crevice revealed no shifts of position of the CAP mass toward the bottom of the aneurysm sac, but slight ballooning of the remnants was observed in two of them. The angiograms of the other four aneurysms with significant crescent crevices demonstrated rupture with a massive hematoma in one and shifts of the CAP mass with marked enlargement of remnants in three. Histologically, the seven aneurysms with no enlarged remnants had newly developed membranes consisting of endothelium, infiltrated spindle-shaped cells, collagen, and elastic fibers. In contrast, in the three markedly enlarged aneurysms, there were only recent clots between the CAP mass and the aneurysm lumen and no development of endothelium. CONCLUSION: Partial thrombosis with CAP solution is useful to keep aneurysms in a stable configuration, unless a crescent crevice has been left.

Aneurysm↗

Purification and characterization of an esterase involved in poly(vinyl alcohol) degradation by Pseudomonas vesicularis PD.

An esterase catalyzing the hydrolysis of acetyl ester moieties in poly(vinyl alcohol) was purified 400-fold to electrophoretic homogeneity from the cytoplasmic fraction of Pseudomonas vesicularis PD, which was capable of assimilating poly(vinyl alcohol) as the sole carbon and energy source. The purified enzyme was a homodimeric protein with a molecular mass of 80 kDa and the isoelectric point was 6.8. The pH and temperature optima of the enzyme were 8.0 and 45 degrees C. The enzyme catalyzed the hydrolysis of side chains of poly(vinyl alcohol), short-chain p-nitrophenyl esters, 2-naphthyl acetate, and phenyl acetate, and was slightly active toward aliphatic esters. The enzyme was also active toward the enzymatic degradation products, acetoxy hydroxy fatty acids, of poly(vinyl alcohol). The K(m) and Vmax of poly(vinyl alcohol) (degree of polymerization, 500; saponification degree, 86.5-89.0 mol%) and p-nitrophenyl acetate were 0.381% (10.6 mM as acetyl content in the polymer) and 2.56 microM, and 6.52 and 12.6 mumol/min/mg, respectively. The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate at a concentration of 5 mM, which indicated that the enzyme was a serine esterase. The pathway for the metabolism of poly(vinyl alcohol) is also discussed.

Amino Acid Sequence↗

Proliferative potential and apoptosis in rat glioma cell lines after hyperthermia.

The proliferative potential of cultured rat glioma cells (C6 and 9L) was evaluated after hyperthermia using immunohistochemical staining with bromodeoxyuridine (BrdU) and Ki-67 monoclonal antibodies. Apoptosis was assessed by in situ end-labeling of deoxyribonucleic acid breaks. Both BrdU and Ki-67 labeling indexes decreased with increasing hyperthermia time. The decrease of the Ki-67 labeling index was not as great as that of the BrdU labeling index. The number of apoptotic cells increased with time after hyperthermia. These results indicate that the antitumor effect of hyperthermia may reflect the induction of apoptosis in the cells within the cell cycle, and the resultant reduction of the proliferative potential of surviving cells, especially in the S phase.

Animals↗

Combined brachytherapy and external beam radiotherapy in normal monkey brains--experimental radiation necrosis evaluated by sequential magnetic resonance imaging.

Radiation-induced brain damage was evaluated using sequential magnetic resonance (MR) imaging in monkeys more than 1 year after either brachytherapy or combined brachytherapy and external beam radiotherapy (EBRT). MR images were obtained 1 week, 1 month, 3 months, and subsequently every 3 months after brachytherapy, and the volume of the lesions was measured. In all four monkeys receiving only brachytherapy and three of the four animals receiving combined brachytherapy and EBRT, MR imaging revealed only transient extensive edema 1 week after treatment and ring enhancement, which was maximal 3 months after treatment, surrounding the implantation site. In one of the four animals undergoing combined brachytherapy and EBRT, MR images obtained 9 months after treatment showed an irregularly extending enhanced lesion with edema. MR images obtained 15 months after brachytherapy in this monkey showed the lesion extended into the contralateral hemisphere through the corpus callosum. Necropsy revealed severe radiation necrosis. This animal developed a very similar MR imaging presentation to that often encountered in human brains after combined brachytherapy and EBRT.

Animals↗

Long-term outcome of surgical treatment of intracavernous giant aneurysms.

A number of approaches have been proposed for the treatment of intracavernous giant aneurysms. In the present study, we have analyzed long-term surgical outcome of 27 consecutive cases of our experience. All the cases were unruptured and symptomatic, showing symptoms such as extraocular movement disorder or visual disturbances. Thirteen cases were male and 14 cases were female. The age of the patients ranged between 11 and 75 years (average 52.2 years) and follow-up periods were between 1 and 20 years (average 7.7 years). Abducens nerve was distributed in 20 cases, oculomotor nerve in 12 cases, optic nerve in six cases, trigeminal nerve in six cases, and trochlear nerve in five cases. In addition to conventional angiography, three-dimensional computed tomographic angiography, balloon test occlusion (BTO), slow injection angiography, aneurysmography, and single photon emission computed tomography with BTO were used to determine a method of treatment. Therapeutic modalities of the present series were as follows: four cases were unoperated, common carotid artery ligation was performed in eight cases, internal carotid artery (IC) ligation in three cases, IC ligation plus superficial temporal artery (STA)--middle cerebral artery (MCA) anastomosis in four cases, IC ligation plus high flow vein bypass in three cases, IC trapping plus STA-MCA anastomosis in three cases, and direct clipping in two cases. Although two cases showed early and late ischemic complications, other cases demonstrated improvement of cranial nerve dysfunction relatively soon after surgical treatment and long-term outcome was generally good. It is concluded that good long-term surgical outcome is obtained for intracavernous giant aneurysms by selecting adequate surgical treatment based upon careful preoperative evaluation of these aneurysms using sophisticated diagnostic methods.

Adolescent↗

Stereotactic brachytherapy for a cystic metastatic brain tumor in the midbrain. Case report.

The authors report a rare case of a cystic metastasis in the midbrain that was successfully treated by brachytherapy following stereotactic biopsy and aspiration of the intratumoral cyst. Stereotactic aspiration of cystic lesions can lead to clinical improvement and brachytherapy prevents cyst recurrence. A 46-year-old man was referred to the authors' institution with a 2-month history of a left hemisensory disturbance and a 1-month history of progressive hemiparesis. Magnetic resonance (MR) imaging revealed a ring-enhancing cystic mass in the midbrain. On the basis of this imaging study, a differential diagnosis that included brainstem abscess, glioma, and metastatic tumor was made. Magnetic resonance imaging-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 5 ml of yellowish-white fluid. Histological examination provided a diagnosis of adenocarcinoma. During the surgery, a catheter through which brachytherapy would be delivered was inserted at a predetermined target. The patient's left hemiparesis and sensory disturbance were markedly improved and brachytherapy was begun 2 days postoperatively. Three radioactive isotopes composed of iridium-192 were implanted to irradiate the tumor tissue. The total dose at the tumor periphery was 30 Gy, which was administered over 100 hours. External-beam radiotherapy (20 Gy) was added after completion of the brachytherapy. At discharge from the hospital, the patient was alert and all his neurological symptoms had resolved. Follow-up MR imaging revealed stabilization of the cyst and no recurrence of the tumor. The patient is alive and well 18 months following the brachytherapy. This case suggests that brachytherapy can delay cyst recurrence, suppress tumor growth, and prolong survival in patients with cystic brainstem metastasis.

Biopsy↗

[Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions].

OBJECTIVE: An extradural temporopolar approach has recently been used in the treatment of the parasellar, infrachiasmatic, or intracavernous regions. In this approach, the temporal (superficial) dural layer is separated from the deep layer (inner cavernous membrane) to expose the cavernous sinus extradurally. We report our experiences with 5 cases in which a giant pituitary adenoma invading the cavernous sinus and parasellar regions was resected via the extradural temporopolar approach. PATIENTS AND METHODS: Between January 1995 and December 1997, 60 patients with pituitary adenomas were operated on at Okayama University Hospital. The extradural temporopolar approach was used for 5 patients who had a giant pituitary adenoma invading the cavernous sinus and parasellar regions. The 5 patients were women aged from 32 to 62 years and presented with a visual dysfunction. Four patients had hormonally non-functioning pituitary adenomas and one had a growth-hormone secreting pituitary adenoma. RESULTS: The operations resulted in 1 total, 3 subtotal and 1 partial removal. There was no operative mortality or major morbidity. Transient oculomotor palsy occurred in 2 cases postoperatively. This approach provided excellent exposure of the tumor, relevant cranial nerves and arteries in and around the cavernous sinus through extradural retraction of the temporal lobe, allowing for sufficient resection of the intracavernous and parasellar portion of the tumor. Tumors invading the inferior portion of the clivus or the contralateral cavernous sinus could not be removed through this approach. CONCLUSION: Our findings suggest that the extradural temporopolar approach is useful for resection of giant pituitary adenomas invading the cavernous sinus and parasellar regions.

Adenoma↗

[Gene transduction for experimental brain tumors using recombinant adenovirus vector].

Recent advances in molecular biology have permitted significant progress toward the treatment of malignant brain tumors using gene transduction methods. Adenovirus vectors have recently been shown to transduce genes successfully into brain tumor cells both in vitro and in vivo. We have investigated the feasibility of gene transduction for brain tumors using adenovirus vectors. To evaluate in vitro transduction rate by adenovirus vectors, rat 9L gliosarcoma cells or human glioblastoma cells were infected with recombinant replication-deficient adenovirus vectors containing the E. coli beta-galactosidase gene (Adex-CALacZ) and stained with X-Gal. We observed a multiplicity of infection (MOI)-dependent rate. Approximately 100% transgene expression was achieved at a MOI of 5 after seven days of incubation. To evaluate transgene expression in a rat brain tumor model, AdexCALacZ was stereotactically injected into established rat 9L brain tumors. Intratumoral injection of AdexCALacZ resulted in high transgene expression in tumor cells. Although injection of AdexCALacZ in the normal basal ganglia resulted in broad and diffuse transduction into endogenous neural cells, direct intratumoral injection resulted in transduction that was relatively restricted to the tumor cells as well as some neighboring normal cells. Transduction rates were relatively elevated at the margin of the tumor. Our results suggest that adenovirus vectors might be a feasible method to transfer therapeutic genes into malignant brain tumors.

Adenoviridae↗

[Primary malignant lymphoma in the central nervous system treated with high dose methotrexate (MTX)-CHOP (M-CHOP)].

From December 1995 to July 1997, six patients with primary malignant lymphoma in the central nervous system were treated with 2 to 5 cycles of the M-CHOP regimen (methotrexate 3 g/m2 on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 40 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and predonisolone 60 mg on day 1 to 14: folic acid was given 3 hours after methotrexate at 10 mg/m2 every 3 hours for 9 doses intravenously). Five patients achieved complete remission (CR) and one experienced partial remission (PR). Posttherapeutic studies were performed in all patients with an average follow-up period of 20.1 months (range 8.1-26.8 months) after confirming the diagnosis. There was no evidence of recurrence of the tumors or growth of residual tumors in any of the patients in this period. The major toxic effect was myelosupression with leukopenia. Alopecia was observed in all patients. No treatment-related deaths were observed. The M-CHOP regimen seems to be a promising treatment for primary malignant lymphoma in the central nervous system.

Adult↗

[A clinical evaluation of combination therapy with radiation, MCNU, carboplatin and IFN-beta or with radiation, MCNU, carboplatin, etoposide and IFN-beta for malignant gliomas].

In this study, we examined the clinical course and prognosis of 32 patients with malignant glioma (17 patients with anaplastic astrocytoma, 15 patients with glioblastoma) treated with the MIC regimen (radiation, MCNU, carboplatin and IFN-beta) or MICE regimen (radiation, MCNU, carboplatin, etoposide and IFN-beta). Ten patients were treated with the MIC regimen and 22 patients with the MICE regimen. The patients treated with the MIC and MICE regimens exhibited no significant difference in clinical background factors. The response rate was 50.0% among the 8 evaluable patients treated with the MIC regimen, and 40.0% among the 20 evaluable patients treated with the MICE regimen. The first- and second-year survival rates for the MIC regimen were 40.0% and 30.0%, and those for the MICE regimen were 68.2% and 36.4%. The overall first- and second-year survivals were 59.4% and 33.9%, respectively. The 50% survival time was 8.6 months for the MIC regimen, 14.9 months for the MICE regimen, and 13.4 months overall. There was no significant difference in response rate or survival period between the group treated with the MIC regimen and that treated with the MICE regimen. Age, histological grade of malignancy, radicality of surgery and total dose of irradiation did not affect length of survival. The only factors significantly related to length of survival were response to the induction therapy and performance of maintenance therapy. These results did not demonstrate the superiority of either the MIC or MICE regimen to other regimens previously reported for the treatment of glioma. In addition, etoposide was found not to improve the efficacy of this type of combined chemoradiation therapy.

Adolescent↗

Long-term enhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian rats with co-grafted polymer-encapsulated human NGF-secreting cells.

The transplantation of genetically modified cells represents one potential means of delivering trophic factors to the brain to support the survival of host neurons and to increase the survival of co-grafted cells. The present study examined the ability of encapsulated baby hamster kidney (BHK) fibroblasts, which were genetically modified to produce human nerve growth factor (hNGF), to provide long-term trophic support to co-grafted adrenal chromaffin cells. Following polymer encapsulation, BHK-hNGF cells were grafted into the striatum of hemiparkinsonian rats together with unencapsulated adrenal medullary chromaffin cells. Secretion of hNGF from the encapsulated cells, morphology of these cells, apomorphine-induced rotational behavior of the host animals, and survival of the co-grafted chromaffin cells were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the BHK cells survived and continued to release hNGF at a level of 2-3 ng/day even 12 months after transplantation. Although the animals receiving adrenal medulla alone did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla intrastriatal hNGF-secreting cells showed a significant decrease (40-50%) in apomorphine-induced rotation within 1 month postimplantation that remained stable for the 12-month test period. Tyrosine hydroxylase immunocytochemistry further revealed that while survival of chromaffin cells without hNGF support was poor, co-grafting of adrenal medulla and BHK-hNGF cells dramatically 926- to 32-fold) increased chromaffin cell survival 1, 6, and 12 months after transplantation. These results demonstrate that (1) encapsulated BHK cells survive for extended periods of time in vivo while continuing to secrete hNGF, (2) the continued secretion of hNGF provides trophic support for co-grafted adrenal chromaffin cells, and (3) the increased chromaffin cell survival is associated with long-term, stable behavioral recovery. These data further support the potential use of this approach for treating Parkinson's disease.

Adrenal Medulla↗

Detection of lipid peroxidation and hydroxyl radicals in brain contusion of rats.

To examine the relationship between the free radicals and brain tissue damage, we investigated the intensity of brain hydroxyl (OH) radical generation and lipid peroxidation in the rat contusion injury model. A unilateral contusion was induced by a weight-drop method. All rats were decapitated six hours after the injury, and brain samples were taken from three portions (core, peripheral, and distal) to examine the specific gravity as an indicator of brain edema, generation of OH using an electron paramagnetic resonance spectrometer (EPR), and malondialdehyde (MDA) and 4-hydroxyalkenals production. Analysis of the specific gravity revealed cerebral edema on the ipsilateral side in the injured group. The signal intensity of EPR in the core and peripheral portions in the contusion group was significantly higher than that in the distal portion of the contusion group and that of all portions in the control animals. No significant difference was observed between the core and peripheral portions of the contusion group. The MDA and 4-hydroxyalkenals production was significantly higher in the core and peripheral portions than in the distal portion of the contusion group and that of all portions of the control group. The degree of posttraumatic brain edema was closely correlated with the increase of DMPO-OH adduct, MDA, and 4-hydroxyalkenals. These results support the current concept that free radical production following traumatic brain injury may induce lipid peroxidation and may be the direct cause of edema formation.

Animals↗

Effects of lecithinized SOD on contusion injury in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic injury, the expression of Cu,Zn-SOD mRNA was examined after contusion in rat using Northern blotting. As determined by specific gravity, lecithinized SOD decreased brain edema. The expression of Cu,Zn-SOD mRNA increased at the core, peripheral and contralateral hemisphere of injury. These increases were then suppressed by lecithinized SOD. Our results support the hypothesis that superoxide may play an important role in edema formation after contusion, and that lecithinized SOD appears to prevent brain edema through a protective effect against superoxide injury.

Animals↗

Accumulation of wild-type p53 in astrocytomas is associated with increased p21 expression.

Approximately one quarter of human astrocytomas show immunohistochemical positivity for p53 protein but lack p53 gene mutations, which could reflect either an accumulation of wild-type p53 protein or an inadequate sensitivity of mutation detection. Since wild-type p53 up-regulates p21 expression, increased p21 expression in those astrocytomas with p53 accumulation in the absence of mutations would argue that the protein was wild type in these tumors. We therefore compared p21 expression with p53 gene and protein status in 48 primary human astrocytomas. Single-strand conformation polymorphism analysis and direct sequencing of the p53 gene showed mutations in 11 tumors (22.9%), while immunohistochemistry revealed positive staining in 19 cases (39.6%). Those tumors with p53 immunopositivity in the absence of p53 mutation had significantly increased p21 expression when compared to either mutant p53 or p53-immunonegative cases. Neither p53 nor p21 status correlated with proliferation indices, as assessed by Ki-67 immunohistochemistry. These results support the hypotheses that functionally wild-type p53 accumulates in some astrocytomas, and that alternative cell cycle checkpoints (such as the p16 pathway) may be more important than p21 in regulating proliferation in astrocytomas.

Adolescent↗

Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1-mediated pathways.

The Saccharomyces cerevisiae crv mutants (crv1, 2, 3 and 4) exhibit phenotypes, such as calcium resistance and vanadate sensitivity, which are apparently similar to those of calcineurin-deficient mutants. We have cloned and characterized the CRV4 gene that complements all the phenotypes of the crv4 mutant. DNA sequencing revealed that CRV4 is identical to the previously cloned gene TTP1, which encodes a type II membrane protein of unknown function. Deletion of CRV4/TTP1 causes no obvious phenotype except for Ca2+ resistance and vanadate sensitivity, but is synthetically lethal in combination with a deletion of MPK1, in a manner which is suppressible by the addition of an osmotic stabilizer. In medium containing sorbitol as an osmotic stabilizer, the enb1 mpk1 ttp1 triple mutant exhibits a more severe growth defect than does any of the double mutants enb1 ttp1, enb1 mpk1 or mpk1 ttp1. A high Ca2+ concentration (50 mM) or a constitutively active form of calcineurin partially suppresses the growth defect of the mpk1 ttp1 double mutant. These results indicate that Ttp1 participates in a cellular event essential for growth and morphogenesis, in parallel with the pathways involving Mpk1 MAP kinase and calcineurin.

Calcineurin↗

Long-term follow-up study of patients with unilateral moyamoya disease.

Although a number of cases of unilateral Moyamoya disease have been reported, the natural history of this disease remains unclear. The clinical features of 17 patients initially diagnosed with unilateral Moyamoya disease at our hospital are reported. Age at onset was 3-45 years (mean, 13.5). Of these 12 cases had onset of symptoms in childhood and five had onset in adulthood. Seven were male and 10 were female. An ischemic attack was the initial episode in ten of the 12 pediatric cases, two of the five adult cases presented with intraventricular hemorrhage. Of the 12 pediatric patients six developed contralateral lesions between 4 and 34 months (mean, 20) after the diagnosis of a unilateral lesion. The remaining six pediatric patients and all adult patients did not develop lesions on the normal side. The mean age at onset for patients later developing contralateral lesions was 6.2 years. The pediatric cases remaining unilateral was 7.7 years. The normal hemisphere of three of the pediatric patients has remained unchanged on repeated follow-up angiograms for over 10 years. Young children tended to develop the vascular pathology bilaterally. However, there were some pediatric cases whose normal or atypical sides remained unchanged without development of bilateral lesions.

Adolescent↗

Long-term results of surgically treated moyamoya disease.

Various surgical procedures have been tried for patients with Moyamoya disease. The most effective treatment, however, is still controversial. We retrospectively evaluated the long-term results of 71 patients (26 men and 45 women) with Moyamoya disease surgically treated in our institute. They consisted of 56 pediatric patients (younger than 15 years) and 15 adult patients. Symptoms in all patients were due to cerebral ischemia. We did 123 operations on 119 hemispheres: 18 superficial temporal artery--middle cerebral artery (STA-MCA) anastomoses, six STA-MCA anastomoses with indirect bypass (IB), 41 encephalo-duro-arterio-synangiosis (EDAS), 29 encephalo-duro-arterio-myo-synangiosis (EDAMS) and 29 ribbon EDAMS. Average follow-up periods for each procedure were: 7 years for STA-MCA anastomosis, 6.2 years for STA-MCA anastomosis with indirect bypass, 11 years for EDAS, 5.6 years for EDAMS and 2.6 years for ribbon EDAMS, respectively. The results of each procedure were satisfactory because the preoperative transient ischemic attacks disappeared. Analysis of follow-up angiograms shows excellent filling of the ACA and MCA territory in the patients undergoing ribbon EDAMS. However, long-term follow-up study shows that about 10% of the patients had severe difficulty in social or school life because of intellectual impairment.

Anastomosis, Surgical↗