Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 19 recordsLinked to original sources

PubMed1995

Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma.

Loci on chromosome 9p are frequently deleted in several malignant tumors, suggesting the presence of putative tumor suppressor genes. The MTS1/p16 and MTS2/p15 genes on 9p are considered to be candidates. Binding of p15 and p16 cell cycle-regulatory proteins to the cyclin dependent protein kinase CDK4 inhibits CDK4/cyclin D dependent phosphorylation of retinoblastoma protein. We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes. We detected losses of one allele and homozygous deletions at loci, including those of the MTS1/p16 and MTS2/p15 genes, in 10 and 3 tumors, respectively. However, we did not detect any tumor-specific mutation in the two genes. The CDK4 gene was amplified in two malignant gliomas without homozygous deletion of the MTS1/p16 and MTS2/p15 genes and one malignant glioma with an allelic loss of the genes. These data suggest that aberrations of the genes coding for components of the cell cycle-regulatory system occurred in at least 15 of 37 gliomas.

Alleles↗

PubMed1995

Differential gene expression of vascular natriuretic peptide receptor subtype in artery and vein.

Although the vasorelaxation by natriuretic peptide (NP) is much less potent in the vein than in the artery, mechanism underlying the phenomenon remains unknown. Since NP receptor consists of three subtypes with different functions, we determined the mRNA level of each NP receptor subtype in the artery and vein by ribonuclease protection assay. In the aorta, NP-A receptor related to the biological action of NP was the predominant form. By contrast, NP-C receptor related mainly to the clearance of NP was the predominant form in the inferior vena cava: NP-C mRNA level was about two fold higher than in the aorta, while both NP-A and NP-B receptor mRNA levels were about half of that in the aorta. These results provide the molecular basis for the different biological response to NP in the artery and vein. Differential gene expression of NP receptor subtype could be an important determinant of the biological actions of NP.

Animals↗

PubMed1995

Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells.

Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic beta cells and is therefore thought to be a potent mediator in the pathogenesis of Type I diabetes mellitus. Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM), attenuates the interleukin-1 beta-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1 beta-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1 beta-induced decrease in ATP content in pancreatic beta cells, suggesting that interleukin-1 beta-induced nitric oxide inhibits the mitochondrial function. The present results show the molecular basis of the preventive effect of high-dose nicotinamide on Type I diabetes mellitus.

Adenosine Triphosphate↗

PubMed1995

Cloning, characterization, and tissue distribution of porcine SPAI, a protein with a transglutaminase substrate domain and the WAP motif.

The primary and gene structures and tissue distribution of porcine SPAI-2, a protein that belongs to the WAP protein superfamily and has a sodium-potassium ATPase inhibitory activity, were determined by molecular cloning and Northern analysis. A full-length cDNA clone was isolated from a porcine duodenum cDNA library. The cDNA insert encoded a polypeptide of 187 amino acids, which is composed of three domains: a hydrophobic presequence of 21 amino acids, a prosegment of 105 amino acids ending with Asp126, and the mature SPAI-2 sequence of 61 amino acids beginning with Pro127. The prosegment contained 16 repeats of a hexapeptide that is highly homologous to the repetitive sequence found in the transglutaminase domain of the human elafin, an elastase-specific inhibitor that also belongs to the WAP superfamily. The repetitive sequence was demonstrated to be a good substrate of transglutaminase using a recombinant preparation produced in Escherichia coli. A porcine genomic library was then screened for the SPAI gene. Characterization and sequencing of positive clones indicated that the gene is similar to the elafin gene, having 3 exons encoding the 5'-untranslated region and signal sequence, proSPAI, and 3'-untranslated region, respectively. Northern blot analysis revealed intestine-specific expression of SPAI mRNA; the message was especially abundant in the small intestine. ProSPAI was also found in the circulation. The similarity of proSPAI to elafin in the domain structure, the acid-labile nature of the cleavage site (Asp126-Pro127), and the fact that the major form of SPAI in the plasma is proSPAI strongly suggest that proSPAI is not the precursor but rather it is the native form of SPAI. Like elafin, therefore, SPAI appears to be a new type of biologically active substance with a transglutaminase substrate domain that acts as an anchoring sequence.

Amino Acid Sequence↗

PubMed1995

Cloning, sequencing, and expression of the dipeptidyl peptidase IV gene from Flavobacterium meningosepticum in Escherichia coli.

The dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) gene from Flavobacterium meningosepticum was cloned by Southern and colony hybridizations using probes amplified by PCR, and expressed in Escherichia coli DH1. E. coli DH1 harboring pFDP-H1, which was a subclone derived from the positive clone pFDP-1, showed 3.5-fold higher activity than F. meningosepticum. Nucleotide sequencing analysis revealed an open reading frame of 2133 bp, coding for a protein of 711 amino acids with a predicted molecular weight of 80,626. The expressed enzyme in E. coli DH1/pFDP-H1 was purified about 345-fold with an activity recovery of 12.3%. The molecular weight of the purified enzyme was estimated to be 75,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 160,000 by gel filtration, respectively, suggesting a dimeric form of the native enzyme. The deduced amino acid sequence of DP IV was homologous to those of the serine proteases of the "prolyl endopeptidase family." A sequence near the C-terminal region and the putative catalytic triad residues were well conserved among these enzymes.

Amino Acid Sequence↗

PubMed1995

Loss of heterozygosity at 11p15 in malignant glioma.

Deletions of loci on chromosome 11p have been found frequently in several malignant tumors including gliomas, suggesting the presence of tumor suppressor genes. We analyzed 38 gliomas [26 malignant gliomas (grades III and IV) and 12 less malignant gliomas (grade I and II)] for loss of heterozygosity using microsatellite sequences on 11p as polymorphic markers. Loss of heterozygosity was found in 8 of 26 malignant gliomas (31%) but not in the less malignant gliomas. In the region with loss of heterozygosity, loci on 11p15.5-pter were commonly deleted. Our results suggest that a putative tumor suppressor gene involved in malignant progression of gliomas is located in an approximately 21-cM region on 11p15.5-pter.

Base Sequence↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗