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Biomedical subjects

T Takeshima

Publications and source records attributed to T Takeshima.

At least 37 records · Page 2Linked to original sources
PubMed2000

Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD.

Plasma homocysteine and cysteine levels were measured in 90 patients with PD with the MTHFR C677T (T/T) genotype. The authors found that the levels of homocysteine-a possible risk factor for vascular disease-were elevated by 60% in levodopa-treated patients with PD, with the most marked elevation occurring in patients with the T/T genotype. Cysteine levels in subjects with PD did not differ from levels in control subjects. In the T/T genotype patients, homocysteine and folate levels were inversely correlated. Increased homocysteine might be related to levodopa, MTHFR genotype, and folate in PD.

Aged↗
PubMed2000

Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, that suggests potential uses of GDNF in the treatment of spinal cord injury and motor neuron diseases. We examined neuroprotective effect of human GDNF encoded by an adenovirus vector (AxCAhGDNF) on the death of lesioned adult rat spinal motoneurons. The seventh cervical segment (C7) ventral and dorsal roots and dorsal root ganglia of adult Fisher 344 rats were avulsed, and AxCAhGDNF, AxCALacZ (adenovirus encoding beta-galactosidase gene) or PBS was inoculated in C7 vertebral foramen. One week after the avulsion and treatment with AxCALacZ, the animals showed expression of beta-galactosidase activity in lesioned spinal motoneurons. Animals avulsed and treated with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal motoneurons and expression of virus-induced human GDNF mRNA transcripts in the lesioned spinal cord tissue. Nissl-stained cell counts revealed that the treatment with AxCAhGDNF significantly prevented the loss of lesioned ventral horn motoneurons 2 to 8 weeks after avulsion, as compared to AxCALacZ or PBS treatment. Furthermore, the AxCAhGDNF treatment ameliorated choline acetyltransferase immunoreactivity in the lesioned motoneurons after avulsion. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury and motor neuron diseases.

Adenoviridae↗
PubMed2000

D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease.

The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Abeta(1-42), is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP(+) toxicity and hippocampal neurons from Abeta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.

1-Methyl-4-phenylpyridinium↗
PubMed2000

Clinical and radiographic evaluation of disc excision for lumbar disc herniation with and without posterolateral fusion.

STUDY DESIGN: A prospective study evaluating the clinical and radiographic results in 95 patients with lumbar disc herniation. OBJECTIVES: To evaluate the results of disc excision, with and without posterolateral fusion. SUMMARY OF BACKGROUND DATA: The effect of posterolateral fusion on the outcomes and radiologic changes in patients with lumbar disc herniation has rarely been reported. METHODS: Forty-four patients underwent disc excision, and 51 patients underwent disc excision and fusion. Clinical symptoms were evaluated using the Japanese Orthopaedic Association Back scores. All medical and surgical records were examined with regard to intraoperative blood loss, operation time, and other data. Preoperative and follow-up radiographs were analyzed to determine the spinal motion and disc height. RESULTS: Clinical outcome was excellent or good in 73% of the nonfusion group and in 82% of the fusion group (P = 0.31). The reduction in lower back pain after surgery was greater in the fusion group. The rate of recurrent disc herniation at the surgical level in the nonfusion group increased, but intraoperative blood loss, operation time, length of hospital stay, and total cost of procedure were all significantly less in the patients undergoing disc excision alone than in the fusion group. The radiologic analysis provided evidence that the disc height at the level of disc excision and posterolateral fusion in the fusion group decreased with time, as in the nonfusion group. The changes in disc height and spinal motion were not related to the clinical results. CONCLUSIONS: Although there is still controversy regarding the pros and cons of fusion in association with disc excision, there is seldom an indication for primary fusion for lumbar disc herniation.

Adolescent↗
PubMed2000

Cosinor analysis of heart rate variability in ambulatory migraineurs.

OBJECTIVE: To clarify whether the circadian rhythm of heart rate variability parameters can be identified in patients with migraine during a headache-free period and to identify any specific pattern of the circadian rhythm of heart rate variability, using time-domain and spectral analysis and cosinor rhythm analysis of heart rate variability during normal daily activity. METHODS: Forty-eight-hour Holter electrocardiograms were recorded for 27 patients with migraine during headache-free periods and 24 healthy controls during free activity. The circadian rhythms of heart rate fluctuation parameters, that is, mean interval, standard deviation, root-mean-square successive differences (RMSSD), %RR50, and low (0. 020 to 0.150 Hz) and high frequency (0.150 to 0.400 Hz) heart rate fluctuations were analyzed with the group mean cosinor method. RESULTS: The group mean cosinor analysis and the acrophase-amplitude analysis demonstrated significant differences in circadian rhythm in SD, RMSSD, %RR50, and high frequency between the group with migraine and controls. The amplitudes of SD, RMSSD, %RR50, and high frequency in the group with migraine were smaller than those in controls, which implied parasympathetic hypofunction in migraineurs. There were no significant differences in the MESOR (midline estimating statistic of rhythms) of the analyzed heart rate parameters except for low frequency. The MESOR of low frequency in the migraineurs was significantly smaller than that in the controls. CONCLUSIONS: Patients with migraine have hypofunction in the parasympathetic nervous system during normal daily activity in the headache-free period.

Adolescent↗
PubMed2000

[A case of superior sagittal sinus thrombosis following long-term medication with carbamazepine].

A 55-year-old man, who had been medicated with carbamazepine, phenobarbital, and sodium valproate for 12 years' duration, presented with severe headache, nausea, and transient diplopia. The neurological examination revealed mild disturbance of consciousness and postural tremor. He also complained of severe continuous headache but no throbbing pain. Enhanced head CT showed empty delta sign and irregular pooling of contrast agent around the superior sagittal sinus. Head MRI did not show the flow void in the superior sagittal sinus. Cerebral angiography demonstrated incomplete occlusion of the superior sagittal sinus and well-developed colateral channels. He was diagnosed having superior sagittal sinus thrombosis, and was placed on anticoagulant and antiplatelet drugs. He did not have any other risk factors such as inflammatory disease, infection, malignancy, and oral contraceptives. However, he had been medicated with some anticonvulsants including carbamazepine, which is known to induce venous thrombosis in the leg. Therefore, the association between superior sagittal sinus thrombosis and long term medication with carbamazepine was suspected. This is the first case report of anticonvulsant-associated cerebral venous thrombosis. It suggests that long-term medication with carbamazepine should be considered to be one of the risk factors for cerebral venous thrombosis.

Anticonvulsants↗
PubMed2000

[A case of anti-GQ1b-positive atypical Fisher syndrome with internal ophthalmoplegia but without external ophthalmoplegia].

We report a 21-year-old man who developed an atypical form of Fisher syndrome. One week after having a common cold, he was admitted to our hospital because of a gait disturbance. Neurological examination revealed a somnolent state, cerebellar ataxia, areflexia, limb muscle weakness, and numbness in a glove and stocking like distribution. The patient had internal ophthalmoplegia but did not have external ophthalmoplegia. Brain MRI showed no abnormality in the orbital and the pretegmental brain regions. The protein level in the cerebrospinal fluid was 57 mg/dl and the cell count was 5 mononuclear cells/mm3. His serum titer of anti-GQ1b IgG antibody was markedly elevated. There have been only two previous reports of isolated internal ophthalmoplegia with elevated anti-GQ1b antibody. The present case suggests that anti-GQ1b antibody play an important role in the pathogenesis of patients who present with internal ophthalmoplegia but without external ophthalmoplegia.

Adult↗
PubMed1999

C1-esterase inhibitor reduces infarct volume after cortical vein occlusion.

In order to clarify the role of complement as a mediator of cerebral infarct growth, we inhibited the classical complement activation pathway in a photochemical cortical vein occlusion model. Immediately after occlusion, rats were infused with either 0.9% saline (vehicle), or C1-esterase inhibitor (C1-INH) over 30 min. Regional cerebral blood flow (rCBF) decreased after occlusion, and was about 50% of baseline after 2 h. No difference was noted between experimental groups. Mean arterial blood pressure (MABP) and arterial blood gases were likewise unaffected by the treatment. However, administration of C1-INH had significantly reduced infarct volume by 72%, as evaluated after 5 days survival. Thus, the neuroprotective effect cannot be explained by an improvement of cerebral perfusion but rather by protection of the parenchyma in the penumbra.

Animals↗
PubMed1999

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females with a mean age of 67.9+/-5.8 years), 12 patients with PSP (eight males and four females with a mean age of 62.6+/-5.8 years) and 36 control subjects (CTL) (16 males and 20 females with a mean age of 65.8+/-9.9 years). The CBD group included patients with probable CBD, while all the patients in the PSP group satisfied the diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP). CSF tau proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). The CSF tau protein level was 320.1+/-86.5 pg/ml in the CBD group, 151.5+/-52.7 pg/ml in the PSP group and 128.7+/-91.7 pg/ml in the CTL group. Significant differences were noted in tau protein levels between the CBD group and both the PSP group (P<0.001) and the CTL group (P<0.005). We suggested that the measurement of CSF tau proteins may be useful for the differentiation between CBD and PSP.

Aged↗
PubMed1999

Low interhemispheric and high intrahemispheric EEG coherence in migraine.

Twenty women with migraine were evaluated by EEG coherence analysis. In comparison with controls, the migrainous subjects showed lower interhemispheric coherence values at C3-C4 for the delta band (P=0.0030) and at F3-F4 (P=0.0055) and C3-C4 (P=0.0018) for the beta band frequency (Wilcoxon criterion). In contrast, 22 intrahemispheric coherence pairs were significantly higher in the migraine group than in the control group (P<0.01). The subjects with visual aura showed lower interhemispheric coherence at O1-O2 and T5-T6 for the alpha band than the subjects without the aura. Discriminant analysis revealed that 95% of the subjects with migraine and 85% of the controls were correctly classified into their proper groups. We suggest that EEG coherence analysis is a sensitive parameter in the detection of electrophysiological abnormalities in patients with migraine.

Adolescent↗
PubMed1999

Branched-chain amino acid therapy for spinocerebellar degeneration: a pilot clinical crossover trial.

OBJECT: The potential effects of branched-chain amino acids (BCAAs) on spinocerebellar degeneration (SCD) were explored in eleven patients. METHODS: The patients received 200 ml of BCAA-rich solution, 2 mg of thyrotropin-releasing hormone (TRH; protirelin), or a placebo daily for 7 days each in a random order. An SCD score was used to quantify the severity of symptoms. PATIENTS: Eleven patients with SCD (7 male, 4 female; mean age 60+/-11; mean disease duration 5.5 years) participated in this study. RESULTS: The mean SCD score of the eleven patients improved significantly by the BCAA treatment compared with the baseline. The conditions of five of the eleven patients (45%) were clearly improved by the BCAA treatment. All of the responders manifested predominantly cerebellar symptoms, but no prominent parkinsonian symptoms. Two patients with marked rigidity and akinesia did not respond to the treatment. CONCLUSION: We concluded that BCAAs do have a beneficial effect on functional improvement in patients with SCD, and that further large scale studies are needed.

Adult↗
PubMed1998

Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B inhibitor.

Both deprenyl and rasagiline (R(+)-N-propargyl-1-aminoindane mesylate), at a concentration of 1-10 microM, increased survival in vitro of rat E14 mesencephalic dopaminergic neurons that had been primed with 10% serum for 12 h (p < 0.05). Rasagiline, but not deprenyl, also increased total neuronal (MAP2-positive) survival (p < 0.05) Under serum-free conditions, rasagiline, but not deprenyl, retained its neuroprotective action on dopaminergic neurones. GABAergic neurons were not affected by either deprenyl or rasagiline. Clorgyline, an MAO-A inhibitor, did not exert any of these effects. The protective action of rasagiline on dopaminergic neurons, even under stringent serum-free conditions, is striking, and warrants further investigation for a role in the treatment of Parkinson's disease.

Animals↗
PubMed1998

Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann-Pick disease type C.

A 15-year-old boy was suffering from splenomegaly and a 10-year history of a neurologic disorder that included mental retardation, vertical supranuclear gaze palsy, dysarthria, ataxia, and dystonia. Bone marrow aspirates revealed foamy cells with storage materials which were positive with filipin staining. Cultured skin fibroblasts derived from the patient showed moderate loss of sphingomyelinase activity and the impairment of cholesterol esterification. The characteristic clinical presentations and typical histochemical findings of this patient met the diagnostic criteria of Niemann-Pick disease type C (NPC). In the fibroblasts from the patient, there was an accumulation of GM2 ganglioside around their cytoplasms. Increased levels of glycolipids. including GM2 ganglioside are reported in the cerebral cortex of NPC, but not in the fibroblasts. The fibroblasts derived from NPC may reflect the abnormal metabolism of glycolipids in the central nervous system of NPC.

Adolescent↗
PubMed1998

Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache.

We examined the lactic and pyruvic acid levels in the plasma of 14 patients with migraine, 17 patients with tension-type headache, and 12 normal controls. The lactic and pyruvic acid levels in the plasma of the migraine patients were significantly higher than those of the normal controls (9.6 +/- 5.0 mg/dL and 0.51 +/- 0.30 mg/dL versus 3.3 +/- 1.9 mg/dL and 0.26 +/- 0.20 mg/dL, respectively). There were no significant differences in the levels between the patients with tension-type headache and normal controls. Our results suggest that migraine patients may have functional abnormalities in mitochondrial energy metabolism.

Adult↗
PubMed1998

Superior sagittal sinus thrombosis: a clinical and experimental study.

Sinus-vein thrombosis is increasingly recognized as a much more frequent neurological disorder than was anticipated before. We examined the pathophysiology of superior sagittal sinus thrombosis (SSST) from 19 patients and a rat SSST model. We treated 19 cases with SSST who were diagnosed by angiography. The symptoms of nine patients, who suffered multiple intracerebral hemorrhage, were abrupt. In another ten patients who recovered satisfactorily, the condition progressed slowly and they were treated with heparin and urokinase. Multivariate analysis demonstrated that female, sudden onset (<24 hours) and posterior 1/3 occlusion are related to bad outcome. Experimentally, SSST was induced by ligation and slow injection of kaolin-cephalin suspension into SSS in rats. Regional cerebral blood flow (rCBF) and tissue hemoglobin oxygen saturation (Hb Sao(2)) using a "scanning" technique were measured at 48 locations, and fluorescence angiography was performed before and until 90 min after SSST induction. After 48 hours the animals were sacrificed for histological studies. Decrease of rCBF and tissue Hb SO(2) and brain damage were seen in group B (n = 10) with an extension of thrombosis from SSS into cortical veins. Brain injury was not observed in group A (n = 8) with SSS thrombus alone and sham-operated animals (n = 5). In conclusion, a brain with acute extension of thrombus from SSS into cortical veins becomes critical for cerebral blood supply and metabolism. CBF, tissue HbSO(2) and repeated angiography can be helpful monitors for the early detection of critical conditions after SSST. As to the therapy, restraint on the ongoing thrombus is essential to protect the brain with SSST, and we encourage the use of combination therapy of heparin and urokinase as early as possible in cases without intracerebral hemorrhage.

Journal Article↗
PubMed1998

An immortalized, type-1 astrocyte of mesencephalic origin source of a dopaminergic neurotrophic factor.

Rat embryonic d 14 (E14) mesencephalic cells, 2.5% of which are glioblasts, were incubated in medium containing 10% of fetal bovine serum for 12 h and subsequently expanded in a serum-free medium using basic fibroblast growth factor (bFGF) as the mitogen. On a single occasion, after more than 15 d in culture, several islets of proliferating, glial-like cells were observed in one dish. The cells, when isolated and passaged, proliferated rapidly in either a serum-free or serum-containing growth medium. Subsequent immunocytochemical analysis showed that they stained positive for GFAP and vimentin, and negative for A2B5, O4, GalC, and MAP2. Serum-free conditioned medium (CM) prepared from these cells caused a fivefold increase in survival and promoted neuritic expansion of E14 mesencephalic dopaminergic neurons in culture. These actions are similar to those exerted by CM derived from primary, mesencephalic type-1 astrocytes. The pattern of expression of the region-selective genes; wnt-1, en-1, sis showed that 70% of the cells were heteroploid, and of these, 50% were tetraploid. No apparent decline in proliferative capacity has been observed after 25 passages. The properties of this cell line, named ventral mesencephalic cell line one (VMCL1), are consistent with those of an immortalized, type-1 astrocyte. The mesencephalic origin of the cell line, and the pattern and potency of the neurotrophic activity exerted by the CM, strongly suggest that the neurotrophic factor(s) identified are novel, and will likely be strong candidates with clinical utility for the treatment of Parkinson's disease.

Animals↗