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Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 451 records · Page 25Linked to original sources

Thrombin and TGF-beta promote human leptomeningeal cell proliferation in vitro.

Some disorders of the central nervous system, such as trauma, meningitis, or subarachnoid hemorrhage (SAH), result in inflammation and fibrosis of the arachnoid membranes followed by hydrocephalus. To clarify the role of growth factors in the pathophysiology of arachnoid fibrosis, we investigated the response of leptomeningeal (LM) cells to growth factors elevated in the cerebrospinal fluid (CSF) of patients with subarachnoidal inflammation. We examined the proliferative responses of LM cells to thrombin, transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), platelet derived growth factor (PDGF), tumor necrosis factor-beta (TNF-beta) and interleukin 1-beta (IL1-beta). Thrombin, TGF-beta, EGF, aFGF and PDGF promoted LM cell proliferation. TGF-beta enhanced the proliferative effect of thrombin and EGF on LM cells. These findings suggest that thrombin and TGF-beta, which may be elevated in CSF following SAH, may cause subarachnoid fibrosis and subsequent hydrocephalus.

Animals↗

The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NF kappa B/Rel.

As examined by the luciferase assay, a negative regulatory region including the NF kappa B motif was found in the 5'-flanking region of the 12-lipoxygenase gene in human erythroleukemia cells. The negative control was abolished by a site-specific mutation of the NF kappa B motif. Probes including the NF kappa B region gave positive bands upon a gel-shift assay. The bands were super-shifted by antibodies for NF kappa B p50, NF kappa B p65 and c-Rel, and were lost by a NF kappa B competitor DNA. Furthermore, the NF kappa B sequence was protected in DNase I footprinting. Thus, two kinds of heterodimer (p50 and p65; p50 and c-Rel) seemed to control the over-expression of the human 12-lipoxygenase gene.

Arachidonate 12-Lipoxygenase↗

Biology of mouse mammary tumor virus (MMTV).

Mouse mammary tumor viruses (MMTV) replicate in the mammary gland, appear as infectious particles in mother's milk and invade the sucking pups from the intestinal tract. The immune system is essential for MMTV in the gut to reach the mammary gland. These properties make the life cycle of MMTV unique. We review the oncologically and immunologically intriguing events caused by MMTV in relation to the life cycle of the virus.

Amino Acid Sequence↗

Dramatic hyperplasia of mtv-2+ lymph node grafts in mtv-2- recipients and selective stimulation of V beta 14+ T cells in recipients' lymph nodes in the DDD mouse.

DDD/1 (DDD) mice contrast strikingly with DDD-mtv-2/mtv-2 (DDD-mtv-2) congenics in their marked lymph node (LN) T cell paucity. To clarify the possible difference in LN function between them, reciprocal LN grafting experiments were conducted. DDD-mtv-2 LN grafts in DDD recipients underwent hyperplasia as dramatic as 10-to 20-fold increase in weight between 3 and 4 wk after implantation. Lymphoid cells in hyperplastic LN grafts were of recipient origin. Similar hyperplasia of mtv-2-heterozygous LN grafts also occurred on various hybrid backgrounds involving DDD mice. Moreover, LN grafts from BALB/c mice infected with mtv-2-derived exogenous mouse mammary tumor virus (MMTV) swelled in MMTV-free BALB/c recipients. Genetic analysis of DDD x (DDD x DDD-mtv-2)F1 backcross progeny demonstrated that LN hyperplasia was closely linked to mtv-2. The frequencies of V beta 5+ and V beta 8+ T cells unresponsive to mtv-2-encoded superantigen (SAg) changed with practically the same kinetics in both LN grafts and recipients' LN. Thus, the cells responsible for LN hyperplasia were polyclonal. V beta 14+ CD4+ cells responsive to mtv-2 SAg were specifically stimulated in recipients' LN but selectively deleted in hyperplastic LN grafts. DDD mice carrying hyperplastic mtv-2+ LN grafts or pretreated with mtv-2+ spleen cells developed an unresponsive state in terms of influx of mtv-2- lymphoid cells into mtv-2+ LN grafts. These results indicate that mtv-2 gene products including SAg may stimulate mtv-2- lymphoid cells of recipients and cause them to migrate into mtv-2+ LN grafts in a nonspecific manner with resulting LN hyperplasia.

Animals↗

Successful chemoradiation therapy for high-grade skull base chondrosarcoma in a child.

High-grade chondrosarcoma in the skull base has been known to be extremely refractory to adjuvant therapy. We report successful chemoradiation therapy for skull base chondrosarcoma in a child. The patient was a 6-year-old boy with an invasive skull base tumor. In spite of gross total removal of the tumor, it recurred 1 month after surgery. Following an intra-arterial injection of adriamycin (10 mg), the second gross total removal was carried out. At the end of the operation, cisplatin (20 mg) was locally injected into the surgical cavity. The patient was further given a total of six courses of systemic chemotherapy in combination with adriamycin (30 mg/m2) and cisplatin (100 mg/m2) and 55 Gy focal irradiation. One year after the most recent surgery, the patient is in complete remission. The efficacy of adjuvant therapy of this rare tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical and angiographic follow-up of childhood-onset moyamoya disease.

To clarify the differences between childhood-onset moyamoya disease and that with onset in adulthood, we studied the clinical course and angiographic findings of adult patients (over 20 years of age) with moyamoya disease of childhood onset (up to 15 years of age). The clinical course in 25 patients could be assessed. The follow-up period was 5-27 years. Neurological deficits were noted in 11/23 and mental disorders in 9/21. In all except one, the illness had started before the age of 7 years. Neither neurological nor mental condition changed during or after adolescence (15-20 years of age). Two patients died of intracranial hemorrhage. The disease progressed in angiographic stage until adolescence, but had stabilized or almost stabilized by the age of 20 years. This study indicates that moyamoya disease with onset in childhood carries high morbidity and mortality. The disease advances in angiographic stage between childhood and adolescence, but stabilizes or almost stabilizes between adolescence and adulthood.

Adolescent↗

Effect of balloon angioplasty on high grade symptomatic vasospasm after subarachnoid hemorrhage.

Of 455 cases of ruptured intracranial aneurysm treated with radical surgery from January 1987 to March 1992, 19 cases with high grade symptomatic vasospasm were treated by percutaneous transluminal balloon angioplasty (PTA). The indication for PTA was high grade symptomatic vasospasm which does not respond to conservative medical treatment. Of the 36 segments of vasospastic arteries, severe vasospasm (angiographical constriction more than 50% of diameter on admission) was observed in 67%. PTA dilated these vasospastic arteries significantly (diameter of more than 75% of diameter on admission) in 83%. Follow up angiography revealed neither recurrence of vasospasm nor chronic atherosclerotic changes. Clinical improvement within 24 hours after PTA was observed in 63% of cases (7 of 17 cases with consciousness disturbance, 5 of 16 cases with motor weakness and one of 7 cases with aphasia). Outcomes at the time of discharge were excellent in 10 cases, good in 3, fair in 4, and lethal in 2. SPECT study before and after PTA confirmed improvement of cerebral blood flow in 3 out of 5 cases investigated. PTA for high grade symptomatic vasospasm after subarachnoid hemorrhage is considered an effective treatment method for the patient who does not respond to medical therapy. Immediate improvement of angiographical and clinical findings were frequently observed immediately after PTA. Exact indication and timing of PTA should be postulated after much more cases have been treated with this methal.

Adult↗

Rate-dependent anisotropic conduction property in the epicardial border zone of canine myocardial infarcts and its modification by moricizine.

We evaluated anisotropic conduction properties, different conduction velocities depending on fiber orientation, in normal and infarcted myocardium and the effects of moricizine on anisotropic conduction. Various cycle lengths of stimulation were applied to 15 mongrel dogs, and epicardial mapping was performed using a 96-channel mapping electrode. Moricizine was then administered to seven dogs and the same procedure was performed. Conduction velocities were calculated from these maps. Programmed electrical stimulations were performed before and after moricizine administration to induce ventricular arrhythmias. Before moricizine administration, a rate-dependent decrease in longitudinal conduction velocity was observed in the infarcted zone. Moricizine suppressed longitudinal conduction in the normal zone significantly at 300 msec pacing, but not at slower rates. Moricizine at a dose of 4 mg/kg, on the other hand, suppressed longitudinal conduction in the infarcted zone significantly at all pacing cycle lengths. The effect of moricizine on transverse conduction was inconsistent. In three dogs, sustained ventricular tachycardia (VT) was induced either before or after moricizine administration. The mean cycle length of sustained VT was prolonged from 202 msec to 291 msec after 4 mg/kg of moricizine. Thus, the changes in cycle length of ventricular tachycardia observed were most likely the result of slowing of conduction velocity, especially in the longitudinal direction, in the infarcted myocardium. We conclude that the electrophysiologic nature of the subacute ischemic model was modified by moricizine, leading to depression of the conduction velocity of longitudinal conduction and the inducibility of ventricular arrhythmias.

Analysis of Variance↗

Clinical application of 18F-FUdR in glioma patients--PET study of nucleic acid metabolism.

Positron emission tomography was used to investigate the metabolism of nucleic acids by 18F-fluoro-2'-deoxyuridine (18F-FUdR) in 22 patients with gliomas. Sixteen cases of high grade glioma clearly demonstrated a region of high activity with a differential absorption rate (DAR) of 0.64 +/- 0.34. Six cases of low grade glioma failed to reveal a positive image of the tumor and the DAR in tumor was 0.21 +/- 0.042 (p < 0.01). This PET-18F-FUdR study succeeded in differentiating high and low grade gliomas from the view point of nucleic acid metabolism.

Adult↗

Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study.

Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.

Arachnoid↗

Development of the brainstem and cerebellum in autistic patients.

Studies of magnetic resonance images have revealed morphological disorders of the brainstem and cerebellum in autistic children and adults. When we studied development of the brainstem and cerebellum in autistic patients, we found that although the brainstem and cerebellum significantly increased in size with age in both autistic patients and controls, these structures were significantly smaller in autistic patients than in controls. The speed of development of the pons, the cerebellar vermis I-V and the cerebellar vermis VI-VII was significantly more rapid in autistic patients than in the controls. However, the speed of development of the other brain structures in the posterior fossa did not differ between autistic patients and controls. The regression intercepts of the brainstem and cerebellum as well as those of their components were significantly smaller in autistic patients than in controls. Results suggest that brainstem and vermian abnormalities in autism were due to an early insult and hypoplasia rather than to a progressive degenerative process.

Adolescent↗

Anaplastic ependymomas: clinical features and tumour suppressor gene p53 analysis.

We analyzed seven cases of anaplastic ependymoma, focusing on neuro-imaging, histopathology, and mutations of the tumour suppressor gene p53. Five of the seven tumours were supratentorial. All had both cystic and solid components, with fragment calcifications detectable on CT scan. The solid parts of the tumours were imaged as heterogenous hypo- or iso-intense areas with moderate enhancement on T1-weighted magnetic resonance images. Vascularity was not prominent on angiograms except for one case. Histologically, in addition to the WHO criteria, loss of typical cellular architecture, endothelial proliferation, and necrosis were commonly found. A mutation in Exon 5 of the tumour suppressor gene p53 was detected in one anaplastic ependymoma out of five tumours (two benign and three anaplastic ependymomas) examined by PCR-SSPC analysis of genomic DNA followed by direct sequencing. Anaplastic ependymoma typically presents as a calcified cystic tumour in the supratentorial parenchyma or transependyma. Mutations of p53 deserve further investigation to examine their possible role in the oncogenesis and malignant transformation of ependymoma.

Adolescent↗

Functional localization of bilateral auditory cortices using an MRI-linked whole head magnetoencephalography (MEG) system.

In 20 healthy subjects, auditory evoked magnetic fields were measured over the entire head, using a helmet-shaped 66-channel MEG system linked to MRI. When the left or right ear was stimulated by 60 msec 2 kHz tones, the prominent 100 msec response (N100m) appeared significantly earlier in the contralateral hemisphere than in the ipsilateral one. In 16 cases, the N100m dipolar field patterns were clear in both hemispheres, overlapping each other across the midline. The N100m sources were estimated using a 2-dipole model in a spherical conducting medium with the size and location of the sphere determined individually according to the MRI images. No differences were found between the contralateral and ipsilateral N100m dipole positions in one hemisphere. When superimposed on MRI, the N100m dipoles were located precisely on the upper surface of bilateral temporal lobes with a standard deviation of 2.2 mm in the superior-inferior direction. In 16 right handed males, the right hemispheric N100m dipoles were 6 mm anterior to the left hemispheric dipoles. The whole head MEG is suitable to see small but significant differences of bilateral cerebral function, with exceptionally high spatial resolution, confirmed by the MRI-linked system.

Adult↗

How to treat incidental cerebral aneurysms: a review of 139 consecutive cases.

BACKGROUND: Together with current advances in neuroimaging techniques, the chance of incidental discovery of unruptured cerebral aneurysms has increased and the selection of their appropriate management remains controversial. To provide current data about management results of patients with incidental cerebral aneurysms, we have made a retrospective review of 139 consecutive patients treated either by surgical or conservative means. METHODS: The surgical indication for each patient was decided, carefully considering several factors respectively, including the surgical difficulty, aneurysm size, patient's age, and medical condition. RESULTS: Forty-nine patients were managed conservatively. Eight (16%) of those conservatively managed patients had intracranial hemorrhage due to aneurysm rupture during the follow-up period (mean, 4.3 years). Seven of these eight patients died from a fatal subarachnoid hemorrhage (SAH). The follow-up data showed that the mean size of aneurysms with late hemorrhage was significantly larger than that of aneurysms without subsequent rupture. It was also confirmed that none of the 26 tiny aneurysms smaller than 4 mm in diameter had ruptured. Ninety patients harboring 119 incidental aneurysms less than 25 mm in diameter underwent surgery. There was no surgical mortality or morbidity in this series. CONCLUSIONS: These excellent surgical results were presumably achieved due to the strict patient selection. In respect to the size of aneurysms, it seems to be justified to recommend surgery for patients with aneurysms larger than 5 mm in diameter.

Adult↗

Percutaneous transluminal angioplasty in a canine model of cerebral vasospasm: angiographic, histologic, and pharmacologic evaluation.

BACKGROUND: Cerebral vasospasm following subarachnoid hemorrhage (SAH) is one of the leading factors that deteriorate the clinical outcome after aneurysmal surgery. Percutaneous transluminal angioplasty (PTA) is a method to directly dilate the constricted vessel using the intravascular neurosurgical technique. METHODS: Angiographic, histologic, and pharmacologic evaluations related to PTA are presented, using a canine double-injection model of SAH. In angiographic evaluation, we studied the effect of PTA performed on day 1, 4, or 7 of SAH. We performed sequential histologic study by light microscopy using the same for the angiographic evaluation. In pharmacologic evaluation, we measured in vitro isotonic constrictive force using two vasoconstrictors immediately after PTA on normal basilar arteries (control group) and basilar arteries on day 7 of SAH. RESULTS: In angiographic evaluation, we observed the effective dilation of spastic artery immediately after PTA and saw no recurrence of vessel constriction when PTA was performed on day 7 of SAH. However, the preventive effect of PTA was inconsistent when it was performed earlier after SAH (days 1, 4). In histologic evaluation, PTA segments immediately after PTA showed denuding of endothelial cells and stretching of the internal elastic lamina without disruption of the muscle layer. In pharmacologic evaluation, there was no difference in isotonic constrictive force created by vasoconstrictors between the PTA and non-PTA segments without SAH. However, there was a statistically significant reduction of isotonic constrictive force on the PTA segment with SAH. CONCLUSIONS: We suggest that the mechanism of PTA vasodilation in vasospasm after SAH may result from mild functional changes in the vascular wall when PTA was applied on day 7 of SAH. The functional changes would not be adequately induced to prevent recurrence of vasoconstriction when PTA was applied soon after SAH.

Angioplasty↗

Should meningiomas involving the cavernous sinus be totally resected?

BACKGROUND: The surgical strategy for meningiomas involving the cavernous sinus (CS) is still controversial because of the difficult surgical approach and the risks of injury to the cranial nerves or the internal carotid artery. We evaluated the efficacy of subtotal removal of meningiomas involving the CS following chemical embolization, preserving cranial nerve functions. METHODS: We analyzed the histology, embolization material, recurrence rate, and neurologic complications in 19 fresh cases with meningioma involving the CS, who received subtotal removal surgery and were followed over 1 year. Patients were 6 men and 13 women aged from 30 to 69 years (mean, 52.2 years) on admission. All patients received preoperative chemical embolization of the feeding arteries to reduce intraoperative bleeding. In the 11 earlier patients, we used estrogen (Est) as the embolization material, but changed to estrogen with 25% alcohol+polyvinyl acetate (Est+PVac) for the latter 8 patients. RESULTS: Fourteen patients were recurrence free after 1-16 (6.5 +/- 5.5) years. The performance status of the survivors was good. Five patients, including two cases of malignant meningioma, developed recurrence, with a mean recurrence-free period of 1.7 +/- 0.5 years. Patients who received embolization with Est showed a higher recurrence rate than Est+PVac. CONCLUSIONS: These results suggest that subtotal resection following Est+PVac embolization is a safe and effective strategy for this tumor.

Adult↗

Proton magnetic resonance spectroscopy of brain in congenital myotonic dystrophy.

Volume selective proton magnetic resonance spectroscopy of brain was performed on a 1.5 T magnet in 5 patients with congenital muscular dystrophy and compared to the results in 46 healthy children and 1 healthy adult. Peaks of N-acetyl aspartate, choline, and creatine but not lactate, were observed in both groups on proton magnetic resonance spectroscopy. Spectroscopy of controls revealed an increase with advancing age in the ratio of N-acetyl aspartate/choline and N-acetyl aspartate/creatine and a decrease in the choline/creatine ratio. In patients with congenital myotonic dystrophy, the N-acetyl aspartate/choline ratio did not increase with advancing age, but the N-acetyl aspartate/creatine ratio did. The choline/creatine ratio decreased with advancing age, which matched the results of controls. At any age older than 4 years, the N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were lower in patients with congenital myotonic dystrophy than in controls. The choline/creatine ratio did not differ between congenital myotonic dystrophy and controls. These results suggest that in patients with congenital myotonic dystrophy N-acetyl aspartate decreases and there exists a developmental disorder of neurons in brain.

Adolescent↗

Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation.

Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was performed with a 1.5T magnet in 28 patients with unclassified mental retardation (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), but not of lactate, were observed in both groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an increase with advancing age in the ratio of NAA/Cho (P = .0031), but no developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower in patients with MR than in controls (P = .0016). The NAA/Cr ratio tended to be lower in the MR group, and the Cho/Cr ratio did not differ between patients with MR and controls. These results suggest that in patients with MR, NAA decreases and a disorder and/or dysfunction of neurons in the brain exists.

Adolescent↗