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Biomedical subjects

Nobuo Hashimoto

Publications and source records attributed to Nobuo Hashimoto.

At least 91 records · Page 5Linked to original sources

MRI and CT findings of neurohypophyseal germinoma.

OBJECTIVE: Magnetic resonance (MR) imaging and computed tomography (CT) findings of neurohypophyseal germinoma have not previously been described in detail. The purpose of the present study was to establish the spectrum of MR imaging and CT findings in neurohypophyseal germinomas. MATERIALS AND METHODS: MR and CT images of 13 consecutive patients (seven males, six females; mean age: 15 years; range: 6-31 years) with neurohypophyseal germinoma were retrospectively analyzed. The diagnosis had been made either histologically (n=8) or clinically according to established criteria (n=5). All patients had been examined using MR imaging and CT before treatment. RESULTS: On MR imaging, infundibular thickening (up to 16 mm) was observed in all 13 cases. Hyperintensity of the posterior pituitary on T1-weighted image was absent in all 13 cases (100%) and 12 of the 13 displayed central diabetes insipidus. Ten germinomas (77%) were isointense to cerebral cortex on T1-weighted image, but variable intensities were exhibited on T2-weighted image. MR images revealed intratumoral cysts in six cases (46%), most of which demonstrated intra-third ventricular extension. Eleven of the 13 cases (85%) revealed hyperdense solid components on unenhanced CT. Calcification was absent in all cases (100%). CONCLUSION: Infundibular thickening, absence of the posterior pituitary high signal on T1-weighted image, lack of calcification and hyperdensity on unenhanced CT are common imaging features of neurohypophyseal germinoma.

Adolescent↗

Early postoperative indicators of late outcome in acromegalic patients.

OBJECTIVE: According to current criteria, normalised serum IGF-1 and glucose-suppressed GH < 1 ng/ml are indicators of biochemical cure in acromegalic patients. We performed a retrospective study to assess whether the attainment of these values in the early postoperative period was predictive of future IGF-1 normalisation and disease inactivity. PATIENTS, MEASUREMENTS AND RESULTS: Between 1978 and 1999, 78 acromegalic patients underwent resection for pituitary adenomas. At the end of the mean follow-up period of 7 years, 43 (55.1%) showed normalised IGF-1 levels and no disease activity. In 51 cases, both IGF-1 and glucose-suppressed GH were examined within the first postoperative month. Of this group, all 19 patients who had early glucose-suppressed GH < 1 ng/ml and were treated by surgery alone maintained normal IGF-1 levels throughout the follow-up; four of them demonstrated delayed (i.e. more than 30 days after the operation) IGF-1 normalisation. In 19 patients with early glucose-suppressed GH levels of 1-4 ng/ml, seven of 11 patients with early normalised IGF-1 and two of eight patients with early IGF-1 elevation manifested eventual IGF-1 normalisation. However, none of the 13 patients with early glucose-suppressed GH > 4 ng/ml attained IGF-1 normalisation. Both univariate and multivariate analyses indicated that early glucose-suppressed GH was a significant factor for predicting late normalised IGF-1; the cut-off value was 1.5 ng/ml (sensitivity: 0.97; specificity: 0.75; odds ratio: 90). CONCLUSION: The attainment of both normalised IGF-1 and glucose-suppressed GH < 1 ng/ml, even during the early postoperative period, suggests absolute cure in acromegalic patients. However, even in patients who do not meet both criteria within the first postoperative month, glucose-suppressed GH < 1.5 ng/ml, or glucose-suppressed GH < 4 ng/ml coupled with early IGF-1 normalisation indicate the possibility of eventual normalisation of IGF-1 and disease inactivity without adjuvant therapy. These postoperative parameters may be useful for assessing the desirability of further treatment.

Acromegaly↗

Intravenous administration of thioredoxin decreases brain damage following transient focal cerebral ischemia in mice.

Thioredoxin (TRX) is induced by a variety of oxidative stimuli and shows cytoprotective roles against oxidative stress. To clarify the possibility of clinical application, we examined the effects of intravenously administered TRX in a model of transient focal cerebral ischemia in this study. Mature male C57BL/6j mice received either continuous intravenous infusion of recombinant human TRX (rhTRX) over a range of 1-10 mg/kg, bovine serum albumin, or vehicle alone for 2 h after 90-min transient middle cerebral artery occlusion (MCAO). Twenty-four hours after the transient MCAO, the animals were evaluated neurologically and the infarct volumes were assessed. Infarct volume, neurological deficit, and protein carbonyl contents, a marker of protein oxidation, in the brain were significantly ameliorated in rhTRX-treated mice at the dose of 3 and 10 mg/kg versus these parameters in control animals. Moreover, activation of p38 mitogen-activated protein kinase, whose pathway is involved in ischemic neuronal death, was suppressed in the rhTRX-treated mice. Further, rhTRX was detected in the ischemic hemisphere by western blot analysis, suggesting that rhTRX was able to permeate the blood-brain barrier in the ischemic hemisphere. These data indicate that exogenous TRX exerts distinct cytoprotective effects on cerebral ischemia/reperfusion injury in mice by means of its redox-regulating activity.

Animals↗

Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors.

Endothelin-1 (ET-1) activates two types of Ca2+- permeable non-selective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC) in Chinese hamster ovary cells expressing endothelin-A receptors (CHOETAR), which couple with Gq, Gs and G12. The purpose of this study was to identify the G proteins involved in the activation of these Ca channels, using mutated ETARs with coupling to either Gq or Gs/G12 (designated ETAR(Delta)385 and SerETAR, respectively) and a dominant negative mutant of G12 (G12G228A). ETAR(Delta)385 is truncated downstream of Cys385 in the C-terminal as palmitoylation sites, whereas SerET(A)R is unpalmitoylated because of substitution of all the cysteine residues to serine (CysCys --> SerSer). ET-1 activated SOCC in CHO-ET(A)R(Delta)385. In CHO-SerET(A)R or CHO-ET(A)R pretreated with U73122, an inhibitor of phospholipase C, ET-1 activated NSCC-1. ET-1 activated SOCC in CHO-ETAR microinjected with G12G228A. Moreover, ET-1 activated NSCC-1 in CHO-ETAR treated with LY 294002, the phosphoinositide 3-kinase inhibitor. These results indicate that NSCC-1 is activated via a G12-dependent pathway, NSCC-2 via Gq/phospholipase C-dependent and G12-dependent pathways, and SOCC via a Gq-phospholipase C-dependent pathway. In addition, NSCC-2 and SOCC are stimulated by ET-1 via a phosphoinositide 3-kinase-dependent cascade, whereas NSCC-1 is stimulated via a phosphoinositide 3-kinase-independent cascade.

Animals↗

Characterization of G proteins involved in activation of nonselective cation channels and arachidonic acid release by norepinephrine/alpha1A-adrenergic receptors.

We demonstrated recently that norepinephrine activates Ca2+ -permeable nonselective cation channels (NSCCs) in Chinese hamster ovary cells stably expressing alpha1A-adrenergic receptors (CHO-alpha1A). Moreover, extracellular Ca2+ through NSCCs plays essential roles in norepinephrine-induced arachidonic acid release. The purpose of the present study was to identify the G proteins involved in the activation of NSCCs and arachidonic acid release by norepinephrine. For these purposes, we used U73122, an inhibitor of phospholipase C (PLC), and dominant negative mutants of G12 and G13 (G12G228A and G13G225A, respectively). U73122 failed to inhibit NSCCs activation by norepinephrine. The magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-alpha1A microinjected with G13G225A were smaller than those in CHO-alpha1A. In contrast, the magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-alpha1A microinjected with G12G228A were similar to those in CHO-alpha1A. In addition, neither a Rho-associated kinase (ROCK) inhibitor nor a phosphoinositide 3-kinase inhibitor affected norepinephrine-induced extracellular Ca2+ influx. G13G225A, but not G12G228A, also inhibited arachidonic acid release partially. These results demonstrate that 1) the Gq/PLC-pathway is not involved in NSCCs activation by norepinephrine, 2) G13 couples with CHO-alpha1A and plays important roles for norepinephrine-induced NSCCs activation, 3) neither ROCK- nor PI3K-dependent cascade is involved in NSCCs activation, and 4) G13 is involved in norepinephrine-induced arachidonic acid release in CHO-alpha1A.

Adrenergic alpha-1 Receptor Agonists↗

A combined subtemporal and transventricular/transchoroidal fissure approach to medial temporal lesions.

OBJECTIVE: To minimize therapeutic morbidity such as cognitive function disturbance and vascular injury to perforating arteries, preoperative functional mapping of the basal temporal lobe functions was performed and the medial temporal lesions were resected via a combined subtemporal and transventricular/transchoroidal fissure approach. METHODS: Twenty-one patients with medial temporal lesions including tumors, arteriovenous malformations, and medial temporal lobe epilepsy underwent operation. The neurovascular structures in the ambient cistern were first dissected free from the medial temporal lobe with a conventional subtemporal approach. Then, the temporal horn was opened through the basal surface of the temporal lobe. Finally, the ambient cistern was accessed from the temporal horn through the choroidal fissure. In five patients whose lesions were revealed to be located on the dominant side by preoperative intracarotid amytal administration test (Wada test), functional mapping of the basal temporal lobe language cortex was monitored for 1 week by use of a subdural electrocorticogram grid before the extirpation surgery. The entrance point from the temporal base to the temporal horn was determined by the result of the functional mapping. RESULTS: The lesions were resected safely and completely in all cases. Language and cognitive functions were preserved even in patients with the basal language area on the dominant side. CONCLUSION: Surgeons can confirm the important neurovascular structures from the subtemporal route and from the transtemporal horn route by a combined subtemporal and transventricular/transchoroidal fissure approach. This approach is especially effective for avoiding ischemic complications by allowing direct confirmation of the anterior choroidal and thalamoperforating arteries.

Adult↗

Use of a large angioplasty balloon for predilation is a risk factor for embolic complications in protected carotid stenting.

Periprocedural neurological complications (PNCs) after carotid stenting were retrospectively analyzed to determine the risk factors with the use of various protective devices. Forty-three lesions in 40 patients were treated by carotid stenting with distal balloon protection for nearly all postdilation procedures and some predilation procedures. The following variables were statistically analyzed for association with PNCs: diameter of the angioplasty balloon used for predilation, use of a distal protection balloon during predilation, use of a protection balloon during postdilation, lesion-bifurcation distance, length of the lesion, age, clinical presentation of the lesion (symptomatic or asymptomatic), and hypercholesterolemia. PNCs occurred in five patients, four with minor deficits and one with major deficits. Univariate analysis showed large diameter of the predilation angioplasty balloon (p = 0.0026), use of a protection balloon during predilation (p = 0.0075), lesion length (p = 0.0003), and lesion-bifurcation distance (p = 0.0006) were significantly associated with PNCs. Multivariate analysis of these four variables showed that use of a large angioplasty balloon for predilation was the only independent predictor (p = 0.004, odds ratio 34.00) for the occurrence of PNCs. Use of a large angioplasty balloon for predilation carries the risk of periprocedural embolic complications. Therefore, even when a protection device is used, predilation should be performed with a small balloon.

Aged↗

Milrinone reduces cerebral vasospasm after subarachnoid hemorrhage of WFNS grade IV or V.

The preventative effect of cisternal irrigation with milrinone against vasospasm was evaluated in 12 patients with subarachnoid hemorrhage (SAH) of World Federation of Neurosurgical Societies grade IV or V treated between September 1999 and September 2000. All aneurysms were clipped or embolized within 72 hours of the onset of SAH. Inlet and outlet tubes were placed in either the supratentorial cisternal space, lateral ventricle, or spinal subarachnoid space. Lactated Ringer solution containing urokinase (120 IU/ml), ascorbic acid (3.5 mg/ml), and milrinone (3.6 microg/ml) was continuously infused at 30 ml/hr for as long as 2 weeks. Angiographical vasospasm was detected in only two of the 11 patients who received milrinone irrigation and underwent postoperative angiography. Vasospasm may have resulted from irrigation obstruction associated with pneumocephalus in one patient and clot in the sylvian fissure in the other patient. The outcome of the milrinone irrigation therapy was significantly better than that of the conventional therapy. This study suggests that cisternal irrigation with milrinone is safe and effective, and reduces the occurrence of vasospasm in patients with poor grade aneurysmal SAH.

Adult↗

Endovascular recanalization of subclavian artery occlusions.

Percutaneous balloon angioplasty for subclavian stenosis achieves satisfactory procedural success rates except for total occlusion. Seven lesions in six consecutive patients who underwent stenting for subclavian total occlusion were reviewed to evaluate the feasibility and efficacy of endovascular stenting. Six lesions were treated using Palmaz stents, and one with the combination of a Palmaz and a SMART stent. Procedural success (residual stenosis < 30%) was achieved for all lesions. The only neurological complication was an embolism in a branch of the posterior cerebral artery, which resulted in homonymous hemianopsia. Follow-up angiography over 6 months after the stenting for five lesions found one in-stent re-occlusion and one ostial restenosis due to elastic recoil. No patient had any new or recurrent symptoms except for recurrent upper limb ischemia due to the case of in-stent re-occlusion during the clinical follow-up period of 1 to 52 months (mean 16.6 months). This complication was resolved by a second treatment. Our limited experience suggests that stenting can redilate even cases of angiographical total occlusion of the proximal segment of the subclavian artery.

Adolescent↗

Involvement of epidermal growth factor receptor-protein tyrosine kinase transactivation in endothelin-1-induced vascular contraction.

OBJECT: Endothelin-1 (ET-1) is one of the major inducers of vasospasm following subarachnoid hemorrhage (SAH). It is generally accepted that extracellular signal-regulated kinase 1 and 2 (ERK1/2) are involved in ET-1-induced vascular contraction. In addition, ET-1 transactivates epidermal growth factor receptor (EGFR) protein tyrosine kinase (PTK), which leads to ERK1/2 stimulation. Therefore, the authors examined whether EGFR-PTK transactivation contributes to ET-1-induced vascular contraction in this study. METHODS: Mitogen-activated protein kinase inhibitor, PD98059, inhibited ET-1-induced ERK1/2 stimulation in rabbit basilar artery (BA) vascular smooth-muscle cells (VSMCs). Moreover, PD98059 inhibited ET-1-induced contraction of rabbit BA rings. A specific inhibitor of EGFR PTK, AG1478, inhibited ET-1-induced EGFR-PTK transactivation, ERK1/2 stimulation, and contraction of BA rings in a concentration-dependent manner. The concentration of AG1478 required for 50% inhibition of the ET-1-induced contraction of BA rings was similar to that for ET-1-induced EGFR-PTK transactivation. Furthermore, AG1478 also inhibited ET-1-induced BA vasospasm in vivo. CONCLUSION: The results indicate that EGFR-PTK transactivation pathway plays an important role in ET-1-induced vascular contraction.

Animals↗

Endotracheal tube electrodes to map and monitor activities of the vagus nerve intraoperatively. Technical note.

Difficulty swallowing due to damage of the vagus nerve is one of the most devastating complications of surgery in and around the medulla oblongata; therefore, intraoperative anatomical and functional evaluation of this nerve is crucial. The authors applied endotracheal tube surface electrodes to record electromyography (EMG) activity from vocal cords innervated by the vagus nerve. The vagal nucleus or rootlet was electrically stimulated during surgery and vocalis muscle EMG activities were displayed by auditory and visual signals. This technique was used successfully to identify the vagus motor nerve and evaluate its integrity during surgery. The advantages of this method compared with the use of needle electrodes include safe simple electrode placement and stable recording during surgery. In cases involving a pontine cavernoma pressing the nucleus or a jugular foramen tumor encircling the rootlet, this method would be particularly valuable. Additional studies with a larger number of patients are needed to estimate the significance of this method as a means of functional monitoring to predict clinical function.

Adolescent↗

Postoperative evaluation of microsurgical resection for cavernous malformations of the brainstem.

OBJECT: The aim of this study was to propose criteria to determine whether complete resection of cavernous malformations in the brainstem had been achieved. METHODS: The authors retrospectively analyzed data in 10 patients harboring a single cavernous malformation who had presented with hemorrhagic symptoms and had been followed up for longer than 2 years postsurgery. The study population consisted of five male and five female patients ranging in age from 13 to 57 years (mean 36.8 years). When preoperative magnetic resonance (MR) images demonstrated the lesion as a homogeneous hyperintense mass, the surgery was defined as complete or incomplete based on intraoperative findings. When preoperative MR images revealed other findings, complete resection was determined according to whether postoperative MR imaging results demonstrated lesions distinct from the peripheral hemosiderin rim. Among the 13 operations in this series, nine resulted in complete resection and were associated with no postoperative clinical relapse of hemorrhage, whereas four operations resulted in incomplete resection and were correlated with postoperative recurrent hemorrhage. The seven patients in whom the outcome of the initial operation was complete demonstrated good neurological recovery in the long-term follow-up period, whereas the three patients in whom the outcome of the initial surgery was judged to be incomplete showed inadequate neurological recovery due to recurrent hemorrhage. CONCLUSIONS: The criteria proposed in this study to evaluate surgical treatment may be a reliable means of predicting the recurrence of hemorrhage postoperatively.

Adolescent↗

Role of primary sensorimotor cortex and supplementary motor area in volitional swallowing: a movement-related cortical potential study.

We investigated the role of the cerebral cortex, particularly the face/tongue area of the primary sensorimotor (SMI) cortex (face/tongue) and supplementary motor area (SMA), in volitional swallowing by recording movement-related cortical potentials (MRCPs). MRCPs with swallowing and tongue protrusion were recorded from scalp electrodes in eight normal right-handed subjects and from implanted subdural electrodes in six epilepsy patients. The experiment by scalp EEG in normal subjects revealed that premovement Bereitschaftspotentials (BP) activity for swallowing was largest at the vertex and lateralized to either hemisphere in the central area. The experiment by epicortical EEG in patients confirmed that face/tongue SMI and SMA were commonly involved in swallowing and tongue protrusion with overlapping distribution and interindividual variability. BP amplitude showed no difference between swallowing and tongue movements, either at face/tongue SMI or at SMA, whereas postmovement potential (PMP) was significantly larger in tongue protrusion than in swallowing only at face/tongue SMI. BP occurred earlier in swallowing than in tongue protrusion. Comparison between face/tongue SMI and SMA did not show any difference with regard to BP and PMP amplitude or BP onset time in either task. The preparatory role of the cerebral cortex in swallowing was similar to that in tongue movement, except for earlier activation in swallowing. Postmovement processing of swallowing was lesser than that of tongue movement in face/tongue SMI; probably suggesting that the cerebral cortex does not play a significant role in postmovement processing of swallowing. SMA plays a supplementary role to face/tongue SMI both in swallowing and tongue movements.

Adult↗

Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms.

BACKGROUND AND PURPOSE: The rupture of a cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanism of its development remains unclear. Inducible nitric oxide synthase (iNOS) is expressed in human and rat cerebral aneurysms, and aminoguanidine, a relatively selective inhibitor of iNOS, can decrease the number of the aneurysms in rats. In this study we applied our new mouse model of cerebral aneurysms to the iNOS gene knockout mice and observed experimental cerebral aneurysms in these animals to elucidate the role of iNOS in the process of cerebral aneurysm formation. METHODS: Eight C57/Bl6 mice and 16 iNOS knockout mice received a cerebral aneurysm induction procedure. Four months after the operation, the mice were killed, their cerebral arteries were dissected, and the region of the bifurcation of the anterior cerebral artery/olfactory artery was examined histologically and immunohistochemically. RESULTS: No significant difference was seen in the incidence of cerebral aneurysms between iNOS+/+ and iNOS-/- mice. However, the size of advanced cerebral aneurysms and the number of apoptotic smooth muscle cells were significantly greater in iNOS+/+ mice than in iNOS-/- mice. CONCLUSIONS: Inducible NOS is not necessary for the initiation of cerebral aneurysm. However, the results of this study suggest that regulation of iNOS may have therapeutic potential in the prevention of the progression of cerebral aneurysms.

Animals↗

Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells.

Recent evidence suggests that adult neural stem/progenitor cells (ANSCs) secrete autocrine/paracrine factors and that these intrinsic factors are involved in the maintenance of adult neurogenesis. We identified a novel secretory molecule, stem cell-derived neural stem/progenitor cell supporting factor (SDNSF), from adult hippocampal neural stem/progenitor cells by using the signal sequence trap method. The expression of SDNSF in adult central nervous system was localized to hippocampus including dentate gyrus, where the neurogenesis persists throughout life. In induced neurogenesis status seen in ischemically treated hippocampus, the expression of SDNSF was up-regulated. As functional aspects, SDNSF protein provided a dose-dependent survival effect for ANSC following basic fibroblast growth factor 2 (FGF-2) withdrawal. ANSCs treated by SDNSF also retain self-renewal potential and multipotency in the absence of FGF-2. However, SDNSF did not have mitogenic activity, nor was it a cofactor that promoted the mitogenic effects of FGF-2. These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system.

Amino Acid Sequence↗

Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice.

Tight junctions are well-developed between adjacent endothelial cells of blood vessels in the central nervous system, and play a central role in establishing the blood-brain barrier (BBB). Claudin-5 is a major cell adhesion molecule of tight junctions in brain endothelial cells. To examine its possible involvement in the BBB, claudin-5-deficient mice were generated. In the brains of these mice, the development and morphology of blood vessels were not altered, showing no bleeding or edema. However, tracer experiments and magnetic resonance imaging revealed that in these mice, the BBB against small molecules (<800 D), but not larger molecules, was selectively affected. This unexpected finding (i.e., the size-selective loosening of the BBB) not only provides new insight into the basic molecular physiology of BBB but also opens a new way to deliver potential drugs across the BBB into the central nervous system.

Animals↗