[Pathophysiological significance of natriuretic peptide receptor].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T Yoshimoto
Publications and source records attributed to T Yoshimoto.
[A case of pineal teratoma arising from hydrocephalus of unknown cause].
We report a case of "functional aqueductal stenosis" which reveals dilatation of the lateral and 3rd ventricles without stenosis at the aqueduct in MRI. This case shows a pineal teratoma which presents one year later with symptoms of hydrocephalus caused by "functional aqueductal stenosis". A seven-year-old boy was admitted to our department owing to headache and vomiting. CT and MRI showed hydrocephalus. The lateral and 3rd ventricles were dilated while the 4th ventricle was normal. Furthermore, tumoral obstruction of the aqueduct was not found. After a ventriculoperitoneal shunt, he recovered well without neurological deficits. One year later, symptoms of precocious puberty, that is the appearance of public hair and deepening of his voice, were found. A follow-up MRI demonstrated a pineal region tumor. Although human chorionic gonadotropin level in the serum and urine was transiently elevated, it normalized before surgery. The operation was performed by the occipital transtentorial approach and the tumor was totally removed. Histological examination proved this tumor to be a mature teratoma, showing three germ cell layers. About two weeks later, he was discharged without any neurological deficit. In this case, although hydrocephalus occurred, MRI didn't demonstrate aqueductal obstruction caused by the tumor. However, one year later, a pineal region tumor was confirmed by MRI. This suggests that hydrocephalus might have some association with the appearance of the pineal region tumor. Therefore, it is necessary to be aware of the possibility of the occurrence of tumors whenever we encounter "functional aqueductal obstruction", when MRI doesn't demonstrate aqueductal obstruction caused by a tumor.
Brain Neoplasms↗
[Ewing's sarcoma at the occipital bone presenting as acute epidural hematoma: a case report].
Primary cranial Ewing's sarcoma is rare. We describe an exceptionally rare case of primary Ewing's sarcoma of the occipital bone, presenting as spontaneous acute epidural hematoma. A 19-year-old female was admitted to our hospital complaining of sudden onset of severe headache. There were no neurological deficit and no abnormal laboratory findings. Computerized tomographic (CT) scan revealed a lentiform shaped high density lesion at the left occipital epidural space. Magnetic resonance imaging (MRI) showed the lesion as iso to low intensity on T1-weighted image (T1WI) and mixed signal intensity on T2-weighted image (T2WI). There were no pathological findings at the adjacent brain. Cerebral angiography demonstrated mass effect. Right occipital craniotomy was performed. We found the tumor arising from the occipital bone and located at the epidural space. The tumor was resected totally. Histological examination revealed the tumor as Ewing's sarcoma with intratumoral hemorrhage. The postoperative course was uneventful. Radiation therapy (50Gy) was given. Follow-up examination six years after the treatment found no evidence of tumor recurrence or distant metastasis. It should be born in mind that primary Ewing's sarcoma of the skull can cause spontaneous acute epidural.
Acute Disease↗
Biomechanical evaluation of hydroxyapatite intervertebral graft and anterior cervical plating in a porcine cadaveric model.
The biomechanical properties of a porous hydroxyapatite (HA) intervertebral graft with or without anterior cervical plating were evaluated in cadaveric porcine cervical spine model using C3-4 discectomy and dissection of the posterior longitudinal ligament to cause instability. The experimental groups were intact (n = 11), instability (n = 11), autogenous bone implant (n = 6), HA graft implant (n = 5), autogenous bone with plating (n = 6), and HA graft with plating (n = 5). Porous HA with 40% porosity and scapular bone were used as grafts. The displacement rates of the cervical spine by compressive forces in the flexural, extensional, and lateral bending directions were evaluated using video-recording followed by computer-assisted analysis. The stiffness to compressive load was calculated from the load-displacement rate curve. The linear and non-linear coefficients of the Fung's equation were obtained based on the plot of Young's modulus against load. There were no statistical differences in the stiffness between the HA and autogenous bone graft in all directions. The two plating groups showed significantly increased stiffness in all directions. The non-linear coefficient value in Fung's equation was far larger in both HA and HA graft with plating groups than in the other groups in flexural compression. Porous HA graft has a compressive strength similar to autogenous graft in vitro, and anterior plating provides additional stiffness to the cervical spine. The larger non-linear coefficient value of the HA groups may represent the characteristic biomechanical brittleness of HA graft, but this is manifest only in flexural compression.
Animals↗
[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy].
Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.
Brain Diseases↗
[A case of malignant rhabdoid tumor in the pineal region in early infancy].
A 6-month-old girl was admitted to another hospital because of consciousness disturbance, preceded by 2 weeks of decreased activity and vomiting. She was referred to our hospital after ventricular drainage had been instituted for hydrocephalus and the tumor in the pineal region. The patient was noted to have conjugate upward gaze palsy and papilledema. CT scan and MRI revealed a large tumor in the pineal region with tumoral hemorrhage and a small mass in the right frontal lobe. At surgery, the pineal region tumor was removed subtotally. Histological examination showed the tumor to be composed of sheets of large polyhedra or round cells with an eccentric round nuclei, prominent nucleoli, and cytoplasmic inclusions. Immunohistochemical studies were positive for GFAP, vimentin, S-100, CK, EMA, and SMA, but negative for AFP, HCG, PLAP, and CEA. Following surgery, she received three 5-day cycles of chemotherapy, consisting of intravenous administration of cisplatin 20 mg/m2/day and etoposide 60mg/m2/day. After these therapies, MRI showed a decrease in the area of high intensity in the pineal region, but almost no change in the right frontal mass lesion. Follow-up radiological examination showed that the tumor had grown rapidly one month after chemotherapy and the patient died 5 months after her first hospitalization. Malignant rhabdoid tumor of the CNS is rare and remarkably malignant. This tumor should be treated using multidisciplinary management with surgery, intensive chemotherapy, and radiotherapy depending on the patient's age.
Brain Neoplasms↗
[Neurophysiological monitoring during surgery for astrocytoma at the motor strip with awake craniotomy].
We present a case of a 26-year-old male with fibrillary astrocytoma at the right face motor cortex. Surgery was performed with the patient under propofol anesthesia. Stimulation mapping techniques for localization of the motor and sensory cortex were applied. The entire right face motor cortex was resected up to the hand region, resulting in a gross total removal of the tumor. Postoperatively, the patient only had transient weakness of the left lower face. For improving the prognosis of gliomas around the motor strip, it is necessary to resect the tumor as much as possible while preserving motor function. Preoperative understanding of the anatomical relationship between the tumor and the motor strip, and intraoprative neurophysiological monitoring may be necessary. In order to simulate the operative fieled preoperatively, we superimposed the superficial venous image obtained by magnetic resonance angiography (MRA) upon the surface anatomy scan (SAS). Magnetoencephalography (MEG) provided precise localization of the central sulcus, preoperatively. The methods of direct cortical stimulation to localize sensorimotor pathways with awake craniotomy enabled us to resect the tumor maximally and to minimize morbidity.
Adult↗
Arachidonate 12-lipoxygenases. Catalytic properties and regulation of the enzyme gene.
Explore the source record for details and available documents.
Animals↗
[Proline specific peptidases].
Explore the source record for details and available documents.
Amino Acid Sequence↗
Total synthesis of MS-444, a myosin light chain kinase inhibitor
Explore the source record for details and available documents.
Journal Article↗
[Reliability and factorial structure of a rating scale for persistent vegetative state].
We developed a new rating scale, Kohnan Vegetative Score, to measure severity and small clinical changes in vegetative state patients. It has 7 items corresponding to the conditions of vegetative state by Japanese Society of Neurosurgery: motor function, food ingestion, urination and defecation, eye movement, vocalization, communication, and facial expression. Each item is rated in 5 ordinal categories: slight (score = 1), mild(2), moderate(4), and extreme(5). The sum of the scores is used as the summary score, which ranges from 7 to 35, and high score means 'severe'. We examined the reliability and the factorial structure of the Kohnan Vegetative Score. The subjects were 10 patients who met the conditions of vegetative state. Four neurosurgeons rated the subjects, and then 2 of them repeated the rating after one week interval. As a measure of reliability, the (weighted) Kappa coefficient proposed Cohen (1960, 1968) was calculated for each item, and the intraclass correlation coefficient (ICC) was calculated for the summary score. To analyze the factorial structure, the factor analysis was carried out. The minimum and the maximum weighted Kappa values were 0.44 and 0.64 for intra-rater reliability, and 0.37 and 0.69 for inter-rater reliability, respectively. Concerning the factorial structure, the contribution of the first factor was 91.5% which indicated the unidimensionality of the scale. The ICC's estimate for the summary score were 0.90 (95% C.I.: 0.766-0.970). On the basis of these results, the Kohnan Vegetative Score has unidimensionality and high reliability enough for a practical use.
Aged↗
In vitro interleukin 12 activation of peripheral blood CD3(+)CD56(+) and CD3(+)CD56(-) gammadelta T cells from glioblastoma patients.
Interleukin (IL)-12 has recently been shown to be directly involved in the activation of natural killer and alphabeta T cells via an IL-2-independent pathway. We show here that another type of human cytotoxic cell, gammadelta T cells activated by solid-phase anti-CD3 antibody and expanded using IL-2, obtained, in this case, from the peripheral blood of glioblastoma patients, displays significant tumoricidal activity. In addition, its cytotoxic activity against K562 or Daudi cells or against autologous glioblastoma targets (but not lymphocytes) is significantly enhanced when costimulated with IL-2 and IL-12. To study this synergistic activation by the two interleukins of the patients' gammadelta T cells, we screened the cells for the presence of the IL-2 receptor (IL-2R) and IL-12 receptor (IL-12R) using both flow cytometric analysis and PCR. The patients' gammadelta T cells constitutively expressed the high-affinity IL-2R; when stimulated with IL-12 plus IL-2, the levels of IL-2Ralpha and IL-2Rbeta increased, whereas that of IL-2gamma did not. They also expressed marginal levels of low-affinity IL-12R both immediately after IL-2 expansion and after 24-h incubation, and significantly higher levels after 72-h incubation, consistent with the level of gammadelta T-cell activation. IL-12 alone induced little proliferation of patients' gammadelta T cells in a 24-h assay and none in a 72-h assay; however, it caused a marked inhibition of the IL-2-induced proliferative response in the 72-h assay. The synergistic action of IL-2 and IL-12 was completely abolished by combined pretreatment with anti-IL-2alpha, beta, and gamma mAbs. IL-12-mediated enhancement of gammadelta T cell cytotoxic activity was inhibited by anti-IL-2Rbeta mAb in a dose-dependent manner but not by anti-IL-2Ralpha or anti-IL-2Rgamma mAbs. Thus, the increased expression of the IL-2Rbeta is critical for the synergistic activation of gammadelta T cells by IL-12 plus IL-2; it is also probable that at least the low-affinity IL-12R contributes to the activation of gammadelta T cells mediated by either IL-12 alone or IL-12 plus IL-2. We have, therefore, demonstrated that IL-12 can stimulate the cytotoxic activity of gammadelta T cells from glioblastoma patients, acting via the IL-2Rbeta component of the IL-2R and low-affinity IL-12R. IL-12 activation of patients' gammadelta T cells could possibly be of potential use in the treatment of glioblastoma patients.
Antigens, CD↗
Enhancement of glucose-induced insulin secretion in transgenic mice overexpressing human VIP gene in pancreatic beta cells.
Using transgenic mice technology, it has now become possible to test directly whether VIP and PHM-27 can enhance glucose-induced insulin secretion and reduce blood glucose in vivo. By microinjecting the entire human VIP gene ligated to the rat insulin II promoter, we have established a mouse model that overproduces VIP and PHM-27 in pancreatic beta cells. VIP was secreted from transgenic islets in a glucose-dependent manner. Analyses of these VIP-transgenic mice indicated that the transgene efficiently enhances glucose-induced insulin secretion and significantly reduces blood glucose as compared with control mice. The transgene also ameliorated glucose intolerance of 70% depancreatized mice. The present results suggest that somatic cell gene therapy directed to diabetic islets by human VIP/PHM-27 gene introduction may provide a means to improve the secretory function of the diabetic islets.
Animals↗
Prolyl aminopeptidase gene from Flavobacterium meningosepticum: cloning, purification of the expressed enzyme, and analysis of its sequence.
In spite of the numerous studies regarding prolyl aminopeptidase, little is known about its mechanism and the significance of its similarity to a number of hydrolases of diverse specificity that belong to the alpha/beta hydrolase-fold family (Pseudomonas 2-hydroxymuconic semialdehyde hydrolase, atropinesterase, and 2-hydroxy-6-oxophenylhexa-2,4-dienoic acid hydrolase; human and rat epoxide hydrolases). We report the cloning and sequencing of the novel prolyl aminopeptidase gene from Flavobacterium meningosepticum (FPAP) which allowed a more comprehensive sequence comparison. FPAP was found to be a 35-kDa monomeric enzyme, releasing N-terminal proline but not hydroxyproline residues from small peptides and naphthylamide esters. Using the unweighted pair group method with arithmetic mean method, an evolutionary tree that depicts the probable relationship between the prolyl aminopeptidases and the alpha/beta hydrolase-fold enzymes was constructed. Since the alpha/beta hydrolase-fold family might also include the members of the prolyl oligopeptidase family (prolyl oligopeptidase, dipeptidyl peptidase IV, and prolyl carboxypeptidase), this proposal links all the known Pro-Y bond-cleaving proline-specific peptidases (prolyl oligopeptidase family, prolyl aminopeptidases, and prolinase) as enzymes with similar scaffolds and hydrolytic mechanisms. On the other hand, the enzymes that cleave X-Pro bonds are metalloenzymes grouped within the "pita-bread" fold family (aminopeptidase P and prolidase). Although the latter two enzymes show significant sequence homology, prolyl aminopeptidase, prolinase, and the members of the prolyl oligopeptidase family do not, and might share the alpha/beta hydrolase-fold scaffold. This rationale would explain the failure in finding a common "proline-recognizing motif" in the primary structures of these proline-specific peptidases.
Amino Acid Sequence↗
IGF2 but not H19 shows loss of imprinting in human glioma.
Genomic imprinting is a gamete-specific modification resulting in the allele-specific expression of genes in somatic cells. A loss of imprinting (LOI) has been found in many embryonal and adult tumors, suggesting that it plays a role in tumor development. The incidence of LOI, however, does not seem to be ubiquitous among tumors because neuroblastoma and colorectal cancer revealed no LOI. We examined the involvement of LOI of IGF2 and H19 genes in human gliomas. The two genes were imprinted in normal brain subcortex tissues. In glioma, 8 of 14 informative cases (57%) revealed LOI in IGF2. The frequency did not depend on the tumor grade. For H19, in contrast, all 13 informative cases maintained imprinting. These results suggest that LOI of IGF2 but not H19 plays a role in the development of human glioma.
Adult↗
A trial to kill tumor cells through Fas (CD95)-mediated apoptosis in vivo.
We tried to induce tumor cell death in vivo through Fas (CD95)-mediated apoptosis. Murine hepatoma MH 134 (Fas-) was transfected with murine Fas antigen cDNA. Fas+ F6b but not Fas- N1d cells underwent apoptosis after treatment with anti-Fas antibody in vitro. The possibility of eradicating tumor cells in vivo with anti-Fas antibody was investigated using double-mutant gld/gld lpr/lpr mice which lack both Fas ligand (FasL) and Fas to avoid cytotoxic activity of the antibody to the liver and interference from endogenous FasL. A single administration of anti-Fas antibody efficiently suppressed the growth of F6b tumors but not that of N1d tumors in these mice. Thus, the therapy with Fas-FasL system may be a promising approach for cancer treatment, and this model is useful for study on in vivo apoptosis-mediated antitumor activity.
Animals↗
Inducible nitric oxide synthase following hypoxia in rat cultured glial cells.
Nitric oxide (NO) produced by inducible nitric oxide (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measuring nitrite. The levels of nitrite produced in the cultured media of glial cells significantly increased after 12-h hypoxia but not after 0- and 6-h hypoxia. The NOS inhibitor, NG-monomethyl-L-arginine, decreased hypoxia-induced nitrite formation. In glial cells after hypoxia/reoxygenation, the iNOS and mRNA and protein expressions were detected by reverse-transcription polymerase chain reaction and by immunocytochemical analysis, respectively. The present study provides the first evidence that hypoxia induces NO production from glial cells. This hypoxia-induced, glial cell-derived NO may play a critical role in the pathogenesis of cerebral ischemia in vivo.
Animals↗
The ipsilateral and contralateral connections of the fifth somatosensory area (SV) in the cat cerebral cortex.
THE ipsilateral and contralateral corticocortical connections to the fifth somatosensory area (SV) in the feline cortex were determined from the location of retrogradely labelled cells following a single injection of HRP into SV. The injection was made into physiologically defined components of the body representation in SV. After injection of HRP into the face regions of SV, HRP-labelled cells were located ipsilaterally in areas 6 beta, 3b and 1-2 of the primary somatosensory (SI), in the second somatosensory (SII), third somatosensory (SIII), and fourth somatosensory (SIV) areas, along the ansate sulcus, and in areas 5a and 6a beta of the ipsilateral cortex, as well as in area 1-2 of SI and in SV of the contralateral cortex. On the other hand, after HRP had been injected into the trunk/hindlimb area, HRP-labelled cells were located in areas 3a, 1-2 of SI, in area 5, in SII, in SIII and in SIV of the ipsilateral cortex, as well as in area 1-2 of SI, and in SV of the contralateral cortex. The extent of these interconnections suggests that SV receives multiple sensory inputs and may function to integrate this information.
Afferent Pathways↗