Biomedical subjects

S Sakaki

Publications and source records attributed to S Sakaki.

At least 37 records · Page 2Linked to original sources

PubMed1999

Changes in visibility of intracranial arteries on MRA with normal ageing.

We investigated age-related changes in the visibility of intracranial arteries on magnetic resonance angiography (MRA) and the influence of risk factors for stroke. We studied 230 adult patients without specific neurological deficits. MRA was performed using the three-dimensional time-of-flight technique with a spoiled gradient-recalled acquisition sequence. We classified internal carotid artery (IC) and the horizontal (M1) and distal (beyond M2) middle cerebral segments into 4 grades. Linear regression revealed a significant negative relation between age and the quality of demonstration on MRA. For IC and M1, the score was significantly lower in subjects with risk factors than in those without. The distal MCA was poorly seen in patients without a history of hypertension or lacunar infarcts. A marked correlation was observed between visibility and age patients with no history of hypertension, diabetes mellitus and hyperlipidaemia. We suggest that atherosclerotic change and decline in flow velocity with normal ageing are factors leading to decreased visibility on MRA.

Adult↗

PubMed1999

Changes in guanylate cyclase activity in arteriolar smooth muscle cells and hemodynamics after ischemia-reperfusion in rats.

Participation of nitric oxide (NO) and hydroxyl radicals in the pathogenesis of hemodynamic alterations after postischemic recirculation were examined by measuring cerebral blood flow (CBF) and estimating guanylate cyclase activities in arteriolar smooth muscle cells using a reversible 2-h thread occlusion model in rats and an electron microhistochemical technique. In the reversible 2-h ischemia model, guanylate cyclase activity in the arteriolar smooth muscle cells increased at the peak of hyperemia and decreased during postischemic hypoperfusion. Administration of N(omega)-nitro-l-arginine (L-NNA), a NO synthase inhibitor, in this model decreased infarct volume and completely inhibited both hyperemia and guanylate cyclase activation at hyperemia. Administration of 1,2-bis(nicotinamido)-propane (AVS), a free radical scavenger, affected neither CBF nor guanylate cyclase activity during hyperemia despite a significant reduction in infarct volume. Administration of L-NNA and AVS significantly suppressed the decrease in CBF during postischemic hypoperfusion and the effect of AVS was greater than that of L-NNA. Although continuous infusion of sodium nitroprusside (SNP) following postischemic hypoperfusion in the reversible 2-h ischemia rats without treatment with L-NNA and AVS did not alter either CBF or guanylate cyclase activity, it significantly elevated both CBF and guanylate cyclase activities in rats administered L-NNA and AVS. The responses of CBF and guanylate cyclase to SNP were also greater in AVS- than L-NNA-treated rats. These results suggest that a physiological vasodilative mechanism is involved in the induction of postischemic hyperemia through the NO-guanylate cyclase pathway in arteriolar smooth muscle cells. Both NO-related and non-related radicals are involved in the pathogenesis of postischemic delayed hypoperfusion through the loss of arteriolar smooth muscle relaxation capability.

Animals↗

PubMed1999

Neurofibromatosis type 2 with multiple primary brain tumors in monozygotic twins.

BACKGROUND: Although monozygotic twins with neurofibromatosis complicated by brain tumors rarely have been reported, none of them fulfilled the diagnostic criteria for neurofibromatosis type 2 (NF2). METHOD: We describe here the first pair of monozygotic twins with NF2, and the result of the molecular analysis of their NF2 gene. RESULTS: One of the brothers (Case 1) developed tetraparesis and cerebellar truncal ataxia at age 12. He had no skin lesions. Radiological examinations revealed, at one time or another, bilateral vestibular schwannomas, a foramen magnum meningioma, five supratentorial meningiomas, and multiple spinal cord tumors. He underwent three operations over a 10-year period to remove tumors. The patient is now 23 years old and is in college. Although asymptomatic when examined at age 12, CT scan revealed that his brother (Case 2) also had multiple brain tumors, including meningiomas, schwannomas, and multiple spinal tumors. Tumors were removed in eight operations over a 10-year period. The patient is now deaf and confined to a wheelchair. An identical nonsense mutation caused by a C to T transition (C169) in a CpG dinucleotide of the NF2 gene was identified in both patients. CONCLUSION: These results led us to speculate that dissimilarities with respect to time of appearance, distribution, and extent of symptoms and tumors between the twins were dependent on the influence of other genetic factors.

Adult↗

PubMed1999

A case of pituitary adenoma associated with McCune-Albright syndrome.

A 11-year-old boy presented with right temporal hemianopsia and was evaluated of a possible pituitary adenoma. At the age of six, he underwent surgery for facial deformities due to fibrous dysplasia. On admission, he had acromegalic features, was 170 cm tall, weighing 66 kg. The left side of his face was slightly deformed, and a café-au-lait spot was found on his right face. Endocrinologic examination revealed elevated basal level of serum GH (103.6 ng/ml, normal < 3 ng/ml) and PRL (259.1 ng/ml, normal < 30 ng/ml). Other endocrine functions were normal. CT showed hyperostosis of the right frontal, occipital, sphenoidal and maxillary bones. Magnetic resonance imaging (MRI) revealed a pituitary macroadenoma with intraadenomatous cyst. On the basis of physical, endocrinologic and neuroradiologic examination, our diagnosis was pituitary adenoma with McCune-Albright syndrome. Surgery was performed by subfrontal approach. By light microscopy, the pituitary tumor represented a typical acidophilic adenoma. Immunoreactivity for GH and PRL were evident in most of the adenoma cells. Double immunostaining for GH and PRL demonstrated the co-existence of the two hormones in a few adenoma cells. However the majority of cells expressed only one hormone. After surgery the right temporal hemianopsia improved. Postsurgical endocrinologic examination revealed reduction in basal serum GH and PRL levels. Administration of bromocriptine decreased blood PRL levels but it had a limited action on GH hypersecretion.

Adenoma↗

PubMed1999

Outcome in acute stroke with successful intra-arterial thrombolysis and predictive value of initial single-photon emission-computed tomography.

This study investigates retrospectively, in selected patients, the ischemic outcome (reversible ischemia, infarction, and hemorrhage) and neurologic outcome of acute stroke treated with intra-arterial thrombolysis and the predictive value of pretreatment single-photon emission-computed tomography (SPECT). Thirty patients with complete recanalization within 12 hours were analyzed. The extent of ischemia was outlined on SPECT, and two CBF parameters were calculated: the ratio of ischemic regional activity to CBF in the cerebellum and the asymmetry index. Reversible ischemia, infarction, and hemorrhage were identified by comparing SPECT and follow-up computed tomography. Nine patients (30%) had no or small infarction, 14 (47%) had medium or large infarction, and seven (23%) had hemorrhage. Forty-two lesions were identified (22 reversible ischemia, 13 infarction, and 7 hemorrhage). Duration of ischemia, urokinase dose, disease type, and occlusion site were nonsignificant factors, whereas neurologic outcome and CBF parameters were significant among the three patient groups and three types of ischemic lesions. Ischemic tissue with CBF greater than 55% of cerebellar flow still may be salvageable, even with treatment initiated 6 hours after onset of symptoms. Ischemic tissue with CBF greater than 35% of cerebellar flow still may be salvageable with early treatment (less than 5 hours). Ischemic tissue with with CBF less than 35% of cerebellar flow may be at risk for hemorrhage within the critical time window. Pretreatment SPECT can provide useful parameters to increase the efficacy of thrombolysis by reducing hemorrhagic complications and improving neurologic outcome.

Adult↗

PubMed1999

An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia.

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Amino Acid Sequence↗

PubMed1999

Endothelial nitric oxide synthase expression in tumor vasculature is correlated with malignancy in human supratentorial astrocytic tumors.

OBJECTIVE: Endothelial nitric oxide synthase (eNOS) may play an important role in the regulation of tumor blood flow and vascular permeability. However, there have been no reports describing alterations of eNOS expression in relation to malignant progression in human astrocytic tumors. We immunohistochemically studied the relationship between eNOS expression in tumor vasculature and malignancy in supratentorial astrocytic tumors. METHODS: Tissue samples were obtained from 12 patients with low-grade astrocytomas, 10 with anaplastic astrocytomas, and 17 with glioblastomas. Normal brain tissue samples were obtained from four patients with other brain diseases. Immunohistochemical staining was performed using the avidin-biotin complex method, with polyclonal anti-eNOS antibody, and the levels of eNOS expression in endothelial cells were evaluated as slight, moderate, or intense on the basis of eNOS immunoreactivity. The proliferative potential was assessed as the MIB-1 staining index for tumor cells. RESULTS: The expression of eNOS was slight in all specimens of normal brain tissue, slight in 7 and moderate in 5 specimens of low-grade astrocytoma, slight in 2, moderate in 6, and intense in 2 specimens of anaplastic astrocytoma, and moderate in 5 and intense in 12 specimens of glioblastoma. The MIB-1 staining index (mean+/-standard deviation) was 0.2+/-0.2% for normal specimens, 1.8+/-0.6% for low-grade astrocytomas, 9.6+/-6.9% for anaplastic astrocytomas, and 18.5+/-7.7% for glioblastomas. The MIB-1 staining indices for slight, moderate, and intense eNOS expression were 2.0+/-2.3%, 10.8+/-9.8%, and 16.9+/-7.7%, respectively. CONCLUSION: Expression of eNOS in tumor vessels was significantly correlated with histological grade and proliferative potential. These findings suggest that astrocytic tumor vessels possess higher activity for nitric oxide production than do normal vessels.

Adolescent↗

PubMed1999

Multivariable analysis of predictive factors related to outcome at 6 months after intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: Recent reports have suggested that a rapid assessment of pretreatment residual cerebral blood flow (CBF) could be used to optimize selection criteria for thrombolysis in patients with acute ischemic stroke to improve clinical outcome. We investigated retrospectively residual CBF and other clinical factors related to outcome at 6 months after intra-arterial thrombolysis by using multivariable analysis. METHODS: Seventy-six patients received intra-arterial thrombolysis within 6 hours of symptom onset. The multiple regression method was used to analyze associations between the modified Rankin scale (MRS) at 6 months after treatment and clinical factors including age, infarction type, duration of ischemia, dose of urokinase, degree of recanalization, hemorrhage, National Institutes of Health Stroke Scale score (NIHSSS), and residual CBF evaluated by pretreatment single-photon emission-computed tomography; these values were assessed with the use of the regional-to-cerebellar activity (R/CE) ratio of ischemic region to cerebellum and asymmetry index. RESULTS: MRS at 6 months was good (0 to 3) in 65% and poor (4 to 6) in 35%. Factors significantly related to MRS at 6 months were R/CE ratio (P<0.0001), NIHSSS at baseline and the following day (P<0.0001), cardioembolic infarction (P=0.0014), age (P=0.0074), and recanalization grade (P=0. 007). NIHSSS of >20, R/CE ratio of <0.35, cardioembolic infarction, incomplete recanalization (grade <3), and older age (>75 years) were determined to be significant independent predictors of poor outcome. CONCLUSIONS: The residual CBF, neurological score at baseline and the following day, age, and recanalization grade correlated significantly with long-term outcome. The NIHSSS of >20 and R/CE ratio of <0.35 were determined to be significant independent predictors of poor outcome by multivariable analysis.

Acute Disease↗

PubMed1999

Greater superficial petrosal nerve neurinoma. Case report.

The authors report a case of middle cranial fossa neurinoma arising from the left greater superficial petrosal nerve in a 21-year-old woman who presented with a left-sided otitis media that chronically recurred over a period of 5 years. On examination, the patient had a left-sided mild conductive hearing impairment and a slight disturbance in tear secretion on the left side, with sensory disturbance in the left palate. Three-dimensional computerized tomography scans clearly demonstrated the enlargement of the foramen lacerum and foramen ovale, and heavily T2-weighted magnetic resonance images revealed the tumor's location along with the course of the greater superficial petrosal nerve and its extension into the tympanic cavity. Following complete surgical excision of the tumor and tympanoplasty via a middle cranial fossa approach, the patient retained useful hearing without facial palsy.

Adult↗

PubMed1999

[Changes in visualization of cerebral MR angiography with normal aging].

MR angiograms from 200 neurologically normal subjects aged 30 to 79 years were analyzed to assess the influence of aging and hypertension on the degree of the--visualization of the cerebral arteries. The degree of MR visualization of the cerebral arteries, including the IC, M 1, and distal MCA, was evaluated on a 4-degree scale. IC and M 1 differ in appearance. The MR gradings of each cerebral arteries showed a significant (p < 0.001) negative correlation with age. Hypertension, which is a risk factors for arteriosclerosis, significantly reduced MR grade. The degree of visualization of M 1 and the distal MCA decreased significantly with age in the normotensive group. Therefore, the decrease visualization of the cerebral arteries appears to involve not only cerebral arteriosclerosis but other factors associated with aging.

Aged↗

PubMed1999

[Cytokine imbalance in critically ill patients: SIRS and CARS].

It remains difficult to treat severely ill patients, especially those who have sepsis and subsequent multiple organ dysfunction syndrome. We propose the hypothesis that the pathophysiology in the sequential sepsis and multiple organ dysfunction syndrome may be strongly related to the imbalance between inflammatory cytokines and antiinflammatory cytokines induced for the host defense to active neutrophils and endothelial cells. Thus we attempted to develop cytokine modulation therapy to normalize the cytokine balance in the host defense system. In this review, we elucidate the relationship between cytokine imbalance and SIRS/CARS in patients with severe burn injury. Furthermore, we examine the possible usage of G-CSF to amplify neutrophil function, and clarify the reasons why various innovative therapies against sepsis have failed.

Critical Illness↗

PubMed1998

Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery.

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.

Animals↗

PubMed1998

Magnetic resonance angiography in patients with acute stroke treated by local thrombolysis.

Although magnetic resonance angiography (MRA) is accepted for showing chronic intracranial stenotic or occlusive lesions, the method has not been practically examined in patients with acute cerebral ischaemia. We carried out three-dimensional time-of-flight MRA in six patients with acute ischaemia treated by local thrombolysis, and compared the findings with those of digital subtraction angiography (DSA). In all patients, MRA before thrombolysis clearly demonstrated the occluded arteries, which corresponded precisely to those shown by DSA. In four patients with complete recanalisation of the occluded vessels after thrombolysis, the recanalisation could be demonstrated by postoperative MRA. In one patient with reocclusion of the recanalised artery, repeat MRA also demonstrated the reocclusion, confirmed by DSA. These results suggest that MRA may be helpful for noninvasive investigation before and after thrombolysis.

Adult↗

PubMed1998

Safety evaluation of Nostoc flagelliforme (nostocales, Cyanophyceae) as a potential food.

The safety of the alga genus Nostoc flagelliforme Born. etFlah. as a human food source was evaluated in an oral acute toxicity study and in a 28-day oral subacute toxicity study using rats. In the acute toxicity study, the dried powder of N. flagelliforme was orally administered to male and female rats at a dose of 1250 mg/kg and 2500 mg/kg. Neither mortality nor changes in general condition were observed in either the study groups or the control group over a 14-day observation period. In the subacute toxicity study, N. flagelliforme powder was administered orally to male and female rats at a dose of 500 mg/kg and 1000 mg/kg for a period of 28 days. Neither mortality nor changes in general condition were observed in either the treatment group or the control group throughout the 28-day administration period. No reduction in food consumption or body weight gain was observed in the experimental animals. Ophthalmological tests performed at the end of the administration period revealed no abnormalities within the ophthalmological parameters. In the haematological tests and serum biochemical tests performed at the time of completion of the administration period, no adverse effects of N. flagelliforme were observed. At autopsy, organ weight at the end of the experimental period and histopathological tests of specimens obtained from the autopsied animals revealed no significant influences of N. flagelliforme. In conclusion, considering the absence of adverse effects of N. flagelliforme in this study, findings in the oral acute toxicity study and the 28-day oral subacute toxicity study may indicate the safety of N. flagelliforme for human consumption. This study is in agreement with the novel nutraceutical idea "Phycophagism".

Animals↗

PubMed1998

Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils.

To evaluate the reversibility of neural function in the brainstem following ischemia, we investigated the effect of transient brainstem ischemia on the brainstem auditory evoked potential in gerbils. Brainstem ischemia was produced by bilateral extracranial occlusion of vertebral arteries. Local cerebral blood flow was measured by quantitative autoradiography after 5 min of ischemia and was reduced to less than 3 ml/100 g per min in the pons and lower midbrain, indicating severe and reproducible brainstem ischemia. During brainstem ischemia, brainstem auditory evoked potential waveforms disappeared completely. After a brief ischemic insult (5 min), all four brainstem auditory evoked potential components recovered to normal. After longer ischemic insults (10-30 min), brainstem auditory evoked potential components never recovered to normal. Microtubule-associated protein 2 immunoreactivity revealed differential vulnerability of the acoustic relay nuclei in the brainstem. Neurons in the lateral lemniscus were most vulnerable, followed in order by neurons in the trapezoid body, the superior olive and the cochlear nucleus. We also demonstrated a close relationship between the reversibility of ischemia-induced changes on brainstem auditory evoked potential and ischemic lesions of these relay nuclei. These data may be useful for evaluating the therapeutic window of thrombolytic therapy during acute vertebrobasilar occlusion.

Animals↗

PubMed1998

Changes in protein synthesis and calcium homeostasis in the thalamus of spontaneously hypertensive rats with focal cerebral ischemia.

The thalamus has been shown to undergo secondary degeneration after cerebrocortical ischemia. However, little is known about the time course of the retrograde thalamic degeneration. The present study was designed to investigate time-dependent changes in the morphology, protein synthesis and calcium metabolism of thalamic neurons in middle cerebral artery (MCA)-occluded spontaneously hypertensive stroke-prone rats that showed primary focal ischemia in the temporoparietal cortex after permanent occlusion of the left distal MCA. In the histologic study by light and electron microscopy, swelling of the nucleus and shrinkage of the perikarya were seen in some neurons of the ventroposterior (VP) thalamic nucleus on the lesioned side at 5 days after ischemia. At the same time, the incorporation of radiolabeled leucine in VP thalamic neurons began to decrease significantly with concomitant a decrease in the number of polyribosomes in the neurons. Conspicuous 45Ca accumulation was noted at 3 days after ischemia and persisted up to 1 month in the VP thalamic nucleus on the lesioned side. These findings suggest that the secondary thalamic degeneration after cortical infarction starts with disruption of calcium homeostasis in situ at the third day after MCA occlusion, followed by a decrease in polyribosomes but not by disaggregation of polyribosomes as seen in hippocampal CA1 neurons subjected to transient forebrain ischemia.

Animals↗

PubMed1998

Impairment in biochemical level of arterial dilative capability of a cyclic nucleotides-dependent pathway by induced vasospasm in the canine basilar artery.

The authors investigated the changes and the potential of cyclic nucleotide-dependent signal transduction, which induces smooth muscle relaxation, in the basilar artery with severe vasospasm in dogs with double experimental subarachnoid hemorrhage (SAH) to explore at which biochemical level the arterial dilative capability was impaired. The amount of cyclic adenosine and guanosine monophosphates (cAMP and cGMP) decreased significantly in the basilar artery after SAH. The activities of adenylate and guanylate cyclases also were decreased significantly in the smooth muscle cells of the basilar artery 4 days after SAH. In addition to the failure of the pathways to produce cyclic nucleotides, the activities of cAMP- and cGMP-dependent protein kinases, which are representative actual enzymes that amplify the signal for vascular dilation, also significantly decreased together with the almost total loss of activation by cyclic nucleotides in the same basilar artery after SAH. It was revealed that the system for smooth muscle relaxation was impaired severely in the cerebral arteries with severe vasospasm after SAH, on the biochemical basis of significantly less vasodilative capability and in several of the steps to produce the cyclic nucleotides of intracellular signal transduction.

Adenylyl Cyclases↗

PubMed1998

Cerebral blood flow measurement as an indicator for an indirect revascularization procedure for adult patients with moyamoya disease.

OBJECTIVE: Some adult patients with moyamoya disease have been treated successfully by indirect revascularization alone, although surgical indications and hemodynamic changes for these patients have not been fully explored. To examine surgical indications for this procedure, we studied the regional cerebral blood flow (rCBF) and angiographic findings in adult patients with moyamoya disease preoperatively and postoperatively. METHODS: On 17 hemispheric sides of 12 adult patients with moyamoya disease treated surgically with a combination of various indirect procedures, mainly by encephaloduroarteriosynangiosis, we retrospectively evaluated changes in rCBF using xenon-133 single photon emission computed tomography, angiographic collateral formation, and clinical results. RESULTS: Preoperatively, the rCBF values in the cortices at the bypass site at rest and after acetazolamide loading were lower than normal. The rCBF values were significantly increased after revascularization, approaching normal, except for incomplete recovery of vascular reactivity. The extent of postoperative neovascularization from implanted tissues fed by the external carotid artery system was more developed, in parallel with the preoperative decrease in resting and loading rCBF values. One-third of the operated sides exhibiting both a low rCBF at rest and impaired vascular reactivity in the noninfarcted cortices achieved good revascularization over two-thirds of the middle cerebral artery territory, accompanied by rCBF improvement and moyamoya vessel regression. Enough potential for neovascularization in the noninfarcted cortices was indicated that the resting rCBF was lower than 50 ml/100 g per minute (below the normal value by 2 standard deviations) and did not increase more than that value after loading, even in a 40-year-old patient who presented with a hemorrhage. Clinically, 11 patients (92%) had good results at the 4-year follow-up, whereas 1 patient (8%) with unsatisfactory neovascularization and a lesser extent of moyamoya vessel reduction experienced rebleeding. CONCLUSION: We conclude that for the surgical treatment of adult patients with moyamoya disease, indirect procedures, mainly encephaloduroarteriosynangiosis, are recommended for patients with lower rCBF and no or negative vascular reactivity in the noninfarcted cortices, as well as for those who have no indication for the direct procedure. It is possible to determine these indications by a xenon-133 inhalation single photon emission computed tomographic study including an acetazolamide challenge test.

Adolescent↗