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Biomedical subjects

T Ohmoto

Publications and source records attributed to T Ohmoto.

At least 55 records · Page 3Linked to original sources

[Herpes simplex type-1 virus-based vectors for gene therapy].

Recent advances in recombinant nucleic acid technologies and the understanding of the molecular biology of diseases provide the basis for gene therapy's ability to impact on the clinical practice of medicine. Herpes simplex virus type 1 (HSV-1) has features that make it suitable as a vector for gene therapy. These properties include: 1) wide host range and high efficiency of gene transfer; 2) large transgene capacity which is provided by deletion of genes unnecessary for viral replication; 3) unique ability of entering a state of latency in neurons; 4) specific oncolytic effect of some mutants by deletion of certain early genes. Three types of vectors designed for gene therapy have been developed from this virus, termed replication-defective vectors, replication-conditional vectors and amplicon vectors. In this review, we describe the recent advances in HSV-1-based vector systems and their applications for gene therapy.

Animals↗

[A case of a scalp arteriovenous fistula associated with Rendu-Osler-Weber disease treated by direct percutaneous embolization].

We present a case of Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia) accompanied by a scalp arteriovenous fistula, which was successfully treated by direct percutaneous embolization. A 51-year-old man, who had multiple vascular telangiectases and pulmonary arteriovenous fistulae, developed an enlarging pulsatile mass of the scalp anterior to the site of the previous craniotomy for a brain abscess in the right occipital lobe. Angiography demonstrated a high-flow arteriovenous fistula between the right superficial temporal artery and a varix. Percutaneous injection of pure ethyl alcohol was planned but seemed risky because of the major drainage being into the bilateral cavernous sinuses through the superior ophthalmic veins. A 24-gauge plastic needle was placed in the right superficial temporal artery just proximal to the fistula, and 0.7 ml of a mixture consisting of n-butyl cyanoacrylate and lipiodol in a ratio of 1:1 was injected. Then, the varix was directly punctured, and retention of the contrast medium was confirmed under manual compression by the placement of a circular ring. Embolization of the varix using 1.0 ml of 70% glucose solution and a subsequent 1.0 ml of pure ethyl alcohol was performed with compression, resulting in total occlusion of the fistula. The scalp mass resolved gradually and there was no evidence of recanalization. We conclude that direct percutaneous embolization is the first therapeutic choice for a scalp arteriovenous fistula with multiple shuntings associated with Rendu-Osler-Weber disease. Dangerous venous drainage should be eliminated before performing embolization with ethyl alcohol.

Arteriovenous Fistula↗

[A case with congenital hydrocephaly and west syndrome who recovered from hypsarrhythmia after the resolution of shunt trouble].

Hydrocephalus occasionally causes West syndrome, but the mechanism is unknown. We experienced a case with West syndrome and congenital hydrocephaly, in which the EEG findings improved after the resolution of shunt complications. The course of this case implied the pathogenesis of West syndrome associated with congenital hydrocephaly, as well as the origin of the seizures and that of the EEG findings in West syndrome. A 7-month-old girl had congenital hydrocephaly. A prenatal diagnosis was made by ultrasonography, and ventricle-peritoneal shunting was performed 7 days after birth. During the following 7 months several shunt replacements were done because of recurrent shunt complications. Her first series of infantile spasms began at the age of 6 months, and treatment was started under the diagnosis of West syndrome. One month later, her seizures were controlled by pyridoxal phosphate, while the EEG still showed hypsarrythmia. Her shunt was then removed again, because of bacterial meningitis due to shunt infection. The recovery from shunt complication resulted in marked improvement of the hypsarrhythmia. Our experience and previous literature suggest the involvement of cerebral cortex in the occurrence of West syndrome associated with congenital hydrocephaly.

Electroencephalography↗

[Neurosurgical therapy for parkinson's disease].

Stereotactic surgery and neuronal transplantation are considered to be effective surgical therapies for advanced Parkinson's disease with wearing off phenomenon. As a stereotactic surgery, posteroventral pallidotomy and chronic pallidal or subthalamic stimulation with inhibitory parameters were performed. Flattening of the motor fluctuations were obtained with improving general motor symptoms especially at "off" time. Therapeutic l-dopa dose could not reduced following pallidotomy and pallidal stimulation, whereas subthalamic stimulation saved 30-50% of l-dopa dose. By the constant supply of dopamine, neuronal transplantation was effective on wearing off. Chromaffin cells of adrenal medulla and pretransected peripheral nerve were cografted into the bilateral caudate nuclei. After the transplantation significant reduction of % time off and l-dopa dose was observed.

Adrenal Medulla↗

Quantitative analysis of growth-related factors in human pituitary adenomas. Lowered insulin-like growth factor-I and its receptor mRNA in growth hormone-producing adenomas.

To elucidate the contribution of growth factors to the development, growth and behavior of human pituitary adenomas, the authors used competitive reverse transcription-polymerase chain reactions to quantify expression of mRNAs for growth factors extracted from pituitary adenomas. As previously diagnosed by endocrinologic evaluation, the pituitary adenomas in this study consisted of six prolactin-producing, six growth hormone (GH)-producing, four follicle-stimulating hormone producing and six nonfunctioning adenomas. The mRNAs examined included those for platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-I and -II; proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation; and pituitary-specific transcription factor-1 (Pit-1) which is a nuclear transcription factor expressed in the anterior pituitary. All factors except the last were expressed in all adenomas, and expression of PDGF B-chain, TGF-beta1, EGF, bFGF and IGF-II did not differ between the four adenoma varieties. Pit-1 was expressed only in GH- and prolactin-producing adenomas. PCNA expression also showed no differences. However, IGF-I mRNA in GH-producing adenomas was significantly lower than in prolactin-producing and nonfunctioning adenomas despite high serum IGF-I levels (1121+/-253 ng/ml). The analysis on IGF-I receptor mRNA was significantly lowered in GH-producing adenoma compared with the other types of adenoma. These findings suggest that the attenuation of negative feedback through the pituitary GH-IGF-I axis may be involved in development of GH-producing adenoma.

Adenoma↗

Primary anorectal malignant melanoma: report of a case.

Primary anorectal malignant melanoma is a fairly uncommon but highly malignant disease. This disease is sometimes mistaken for such benign conditions as either a hemorrhoid or rectal polyp. We herein describe a case of early primary malignant melanoma of the anal canal. In this case, magnetic resonance (MR) imaging was found to be useful for diagnosing the melanotic melanoma. We especially emphasize the usefulness of a fat-saturation MR image in distinguishing melanotic melanoma from other rectal tumors.

Aged↗

Cerebral gangliogliomas: clinical characteristics, CT and MRI.

Eight patients with ganglioglioma who received surgical treatment at our institute between January 1989 and January 1997 were reviewed to determine their clinical, CT and MRI characteristics. Tumours were located in the temporal lobe (four patients), trigone of the lateral ventricle (two patients), basal ganglia (one patient) and fronto-temporal lobe (one patient). On imaging, two types of tumours were seen, a solid mass in 5 patients (62.5%) and a cystic mass in three patients (37.5%). Six complete tumours (75%) and all of the solid components of the cystic tumours were enhanced by contrast medium. Seven tumours (88%) had no peripheral oedema. On CT, the tumours being studied appeared as iso-(62.5%) or low density (37.5%) intra-axial tumours. Four tumours (50%) contained calcification. On MRI, the tumours appeared as well-circumscribed, iso-(62.5%) or low intensity (37.5%) intra-axial tumours on T1 weighted images, and as high (75%) on T2 weighted images. Three underwent total resection, 2 subtotal resection and 3 partial resection. No patients had have any further treatment such as radiation therapy or chemotherapy. Postoperative studies were conducted on all patients with an average follow-up period 56 months (range 4-147 months) after surgery. There was no evidence of recurrence of tumours or of growth of residual tumours. We observed gangliogliomas which were located in unusual regions such as the trigone in two of the patients. To our knowledge, our series is the first report to describe trigonal gangliogliomas. We conclude, therefore, that ganglioglioma should be included as a possibility in the differential diagnosis of intracranial masses, even when they are located in the trigone.

Adolescent↗

Experimental study of intracisternal administration of tissue-type plasminogen activator followed by cerebrospinal fluid drainage in the ultra-early stage of subarachnoid haemorrhage.

This experimental study evaluated the effect of intrathecal injection of tissue-type plasminogen activator followed by cisternal drainage in the ultra-early stage of aneurysmal subarachnoid haemorrhage to prevent vasospasm. Twenty Japanese white rabbits were divided into five groups. Either tPA (groups A, B, and E) or saline (groups C and D) was injected intrathecally 1 hour (groups A, B, C, and D) or 21 hours (group E) after the intrathecal injection of blood. Cerebrospinal fluid was drained 2, 4, and 6 hours after the intrathecal injection of blood (groups A, C, and E). On day 4, the angiographic caliber of the basilar artery in each group was as follows (mean +/- SD): A, 85.9 +/- 5.0%; B, 74.6 +/- 5.3%; C, 69.1 +/- 2.7%; D, 64.0 +/- 4.9%; E, 80.2 +/- 2.7% (compared with baseline). In the two groups in which CSF was drained (groups A and C), fibrinolysis with tPA significantly suppressed vasospasm. In the two groups treated with tPA (groups A and B), cisternal drainage significantly suppressed vasospasm. In the two groups treated with saline (groups C and D), however, cisternal drainage did not suppress vasospasm. Examination of the series of CSF samples (groups A and C) showed that fibrinolysis with tPA effectively cleared clots early. In the two groups treated with tPA and CSF drainage (groups A and E), early removal of subarachnoid clots reduced the degree of vasospasm. Early fibrinolysis with tPA and early removal of subarachnoid clots by drainage is effective for preventing vasospasm.

Angiography, Digital Subtraction↗

Dipole analysis in a case with tumor-related epilepsy.

In order to evaluate the effectiveness of presurgical dipole analysis of interictal spikes as a non-invasive technique for the determination of epileptogenic area, we compared the results of this method with those of electrocorticography (ECoG) localization in the diagnosis of a patient with tumor-related epilepsy. A preoperative MRI revealed a temporal lobe tumor on the right side. The individual dipoles estimated from the interictal spikes were located mainly in the anterolateral region of the right temporal lobe, although some were located in the mesial side. The ECoG recorded frequent spikes in the anterolateral region of the right temporal lobe consistent with the location estimated by dipole analysis. After surgery, the patient suffered from residual seizures. Therefore, the residual epileptogenic area was examined by dipole analysis using a four-layered head model instead of the previous three-layered head model. As a result, the dipole analysis was able to pinpoint the epileptic focus in the area directly adjacent to the resected area, and in the mesial temporal lobe. In conclusion, EEG dipole analysis appears to hold promise as a non-invasive presurgical evaluation technique for locating epileptogenic areas as well as for postsurgical evaluation of residual epileptic focus.

Adolescent↗

Neural transplantation for Parkinson's disease.

1. Neural transplantation is one promising approach for the treatment of Parkinson's disease. Fetal substantia nigra cells are a good source of dopamine, but in order to avoid ethical and immunological problems, adrenal medullary chromaffin cells have been investigated as an alternative source. 2. Grafted adrenal medullary chromaffin cells can provide dopamine as well as several neurotrophic factors that affect dopaminergic neurons in the brain. 3. We review experimental studies for application of neural transplantation techniques in Parkinson's disease, including immunological studies, cryopreservation, microvasculature, donor tissue, and direct gene delivery studies performed in our laboratory. Our clinical experience and new approach involving a polymer-encapsulated cell grafting procedure are also described.

Animals↗

A giant thrombosed aneurysm of the petrous carotid artery presenting with cavernous sinus syndrome: case report.

Aneurysms involving the petrous Carotid artery are rare and a review of the literature demonstrates that the mode of clinical presentation depends on the direction of expansion of the aneurysmal sac. The eighth nerve is the most commonly affected, followed by the fifth nerve, sixth nerve and seventh nerve, respectively. There has not been reported to date a lesion presenting with cavernous sinus syndrome. We present the case of a 46-year-old woman who complained of left facial pain and pan-ophthalmoplegia, and was shown to have a giant thrombosed aneurysm of the petrous carotid artery extending into the cavernous sinus. Because preoperative evaluation of the patient revealed good collateral flow, proximal balloon occlusion of the left internal carotid artery was performed. Neurological symptoms of the patient resolved 2 months after surgery except for the size of the left pupil. We conclude that an aneurysm of the petrous carotid artery should be included in the differential diagnosis of cases presenting with a cavernous sinus syndrome. Early diagnosis followed by definitive treatment is important for the alleviation of clinical symptoms associated with this lesion.

Case Reports↗

Embolization of cerebral arteriovenous malformations with cellulose acetate polymer: a clinical, radiological, and histological study.

OBJECTIVE: A cellulose acetate polymer (CAP) solution was hypothesized to be useful for the embolization of arteriovenous malformations (AVMs). To investigate this possibility, we analyzed the clinical, radiological, and histological results of patients with AVMs embolized by using a CAP solution. METHODS: We reviewed the cases of 11 patients with AVMs treated by embolization before surgical resection. We used two types of CAP solutions, CAP-M and CAP-L, which are mixtures of 250 mg of solid CAP and 1800 or 2250 mg of bismuth trioxide dissolved in 5.5 or 7.0 ml of dimethyl sulfoxide, respectively. After the embolization procedure, percent reduction of the nidus volume was measured, and thereafter, the clinical course and computed tomographic scans and/or magnetic resonance imaging scans were evaluated. All patients underwent surgical resection 1 to 51 days after embolization. Resected specimens were stained for light microscopic examination. RESULTS: Thirty-nine feeding vessels were embolized. The reduction rate of the nidus volume ranged from 20% to nearly 100%. Transient and persistent ischemic deficits occurred in three patients and one patient, respectively, and there were no hemorrhagic complications. All AVMs but one were completely resected by surgery. The embolized AVMs were soft enough to be easily cut and retracted. The histological examinations disclosed no or mild inflammatory reactions within 2 weeks after embolization. The internal elastic lamina was preserved in every case. Recanalization through the cast of the CAP mass was not observed until 51 days after embolization. CONCLUSION: CAP solution is a safe and useful embolic agent for AVMs.

Adult↗

Purification and characterization of an esterase involved in cellulose acetate degradation by Neisseria sicca SB.

An esterase catalyzing the hydrolysis of acetyl ester moieties in cellulose acetate was purified 1,110-fold to electrophoretic homogeneity from the culture supernatant of Neisseria sicca SB, which can assimilate cellulose acetate as the sole carbon and energy source. The purified enzyme was a monomeric protein with a molecular mass of 40 kDa and the isoelectric point was 5.3. The pH and temperature optima of the enzyme were 8.0-8.5 and 45 degrees C. The enzyme catalyzed the hydrolysis of acetyl saccharides, p-nitrophenyl esters of short-chain fatty acids, and was slightly active toward aliphatic and aromatic esters. The K(m) and Vmax for cellulose acetate (degree of substitution, 0.88) and p-nitrophenyl acetate were 0.0162% (716 microM as acetyl content in the polymer) and 36.0 microM, and 66.8 and 39.1 mumol/min/mg, respectively. The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate, which indicated that the enzyme was a serine esterase.

Amino Acid Sequence↗

Effect of intracarotid infusion of etoposide: modification of the permeability of the blood-brain barrier and the blood-tumor barrier in rat brain tumor model.

The effect of intracarotid infusion of etoposide on the permeability of the blood-brain barrier (BBB) and brain-tumor barrier (BTB) was investigated using a model of rats injected with C6 glioma cells. Fifty four glioma-bearing rats were divided into 3 groups and treated with 0, 3, or 15 mg/kg of etoposide infused into the internal carotid artery. BBB or BTB permeability was evaluated qualitatively by the leakage of Evans blue (6 animals in each group) or quantitatively by the diffusion of carboplatin [cis-diammine (1,1-cyclobutane-dicarboxylato) platinum(II); CBDCA] (12 animals in each group) into the normal brain or the tumor tissue. BBB and BTB disruption augmented significantly in proportion to the dose of etoposide. The degree of disruption of BTB was greater than that of BBB, but the rate of disruption of BBB in proportion to increasing the dose of etoposide was higher than that in the BTB. Histopathologically, no obvious changes were observed in the animals of either the control group or the 3 mg/kg group but degenerative changes in the neurons of the hippocampus of the infused hemisphere were seen in the 15 mg/kg group. This change is thought to be caused by apoptosis because of the positive reaction with TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide. Therefore, the dosage of etoposide for intracarotid infusion should be lower than 15 mg/kg in order to reduce neurotoxicity of both etoposide and concurrent anticancer drugs.

Animals↗

Suitable image parameters and analytical method for quantitatively measuring cerebral blood flow volume with phase-contrast magnetic resonance imaging.

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.

Adult↗

Proliferative potential of malignant glioma cells before and after interstitial brachytherapy.

The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examination of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6 +/- 5.5%, and that of the primary tumors was 17.0 +/- 11.2%, showing a significant difference (p < 0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells.

Adult↗