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Biomedical subjects

G Maeda

Publications and source records attributed to G Maeda.

At least 19 recordsLinked to original sources

Ganglion cells in Ewing's sarcoma following chemotherapy: a case report.

A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported. The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation. The patient received combined intensive multi-drug chemotherapy and radiation before surgery. Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes. An immunohistochemical study revealed that neural differentiation was enhanced. Immunoreactivity for Leu-7 also became positive. Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months after the diagnosis. Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen in the biopsy samples, but associated with prominent Homer-Wright rosettes. To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after pre-operative chemotherapy and radiotherapy.

12E7 Antigen

Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson's patients with severe postural instability and gait disorders.

Postural instability and gait disorders (PIGD) are the primary causes of disability in many but not all advanced Parkinson's disease (PD) patients. We have measured the concentrations of serotonin, 5-hydroxytryptophan (5-HTP), 5-hydroxy-3-indoleacetic acid (5-HIAA), and homovanillic acid (HVA) in samples of ventricular cerebrospinal fluid from ten PD patients with severe disability from PIGD and from ten PD patients with tremor and levodopa induced dyskinesia as their predominant motor dysfunction. The two groups were prospectively matched for duration of disease and age. No significant differences between the two groups were found in the concentration (mean +/- SD in ng/ml, PIGD dominant vs. tremor-dyskinesia dominant) of 5-HIAA (106 +/- 50 vs. 99 +/- 34) or HVA (1,068 +/- 595 vs. 881 +/- 469). Serotonin concentration was significantly lower (0.7 +/- 0.5 vs. 1.5 +/- 0.9) and 5-HTP concentration was substantially higher (684 +/- 1,054 vs. 6 +/- 5) in the patient group with PIGD as their predominant symptoms. Thus, the distinguishing feature of patients with severe PIGD appears to be a derangement in indoleamine metabolism at the reaction step catalyzed by aromatic amino acid decarboxylase (AADC). These findings suggest that aggravation of PIGD in advanced Parkinson's may be related in part to impaired serotonergic transmission secondary to inhibition or down regulation of AADC.

5-Hydroxytryptophan

Electrophysiologic target localization in posteroventral pallidotomy.

The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications. Using a 1.8 x 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 degrees above base plane, 20 degrees from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P < .0001) and visual (P < .0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2-3 mm, and 4-5 mm proximal to Tf were also statistically significant (P < .0001). Microelectrode recording to electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patterns providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract. Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.

Adult

Endothelium-dependent vascular smooth muscle relaxation activated by electrical field stimulation.

Electrical field stimulation (EFS) produced relaxation of contracted arteries in the presence of tetrodotoxin. In the present study the contributions of vascular smooth muscle repolarization and endothelial release of nitric oxide to the relaxation response were investigated using isolated rat tail arteries and bovine aortic endothelial cells (BAEC). Intact and endothelium-denuded rings or intact, pressurized artery segments were contracted with either phenylephrine or KCl prior to EFS. Electrical field stimulation induced a small relaxation in denuded, phenylephrine contracted rings that was inhibited by the K+ channel blockers glibenclamide and BaCl2. In intact, phenylephrine-contracted rings, EFS induced significantly larger relaxations that were inhibited by BaCl2 as well as by L-NAME, an inhibitor of nitric oxide (NO) synthase, and methylene blue. EFS-induced relaxations were completely inhibited when BaCl2 and L-NAME or methylene blue were combined. Exposure to Ca(2+)-free buffer or diltiazem also inhibited the relaxation while ascorbic acid had no effect. Effluent from electrically stimulated BAEC caused denuded, phenylephrine contracted rings to relax. The ability of the effluent to cause relaxation was almost completely blocked by exposure of the BAEC to L-NAME or exposure of the recipient vascular smooth muscle to methylene blue; glibenclamide caused partial blockade. Simultaneous measurements of membrane potential and intraluminal pressure showed that EFS-induced membrane repolarization preceded changes in steady-state pressure. It is concluded that (1) the smooth muscle cells possess an endothelium-independent repolarization mechanism, (2) EFS causes endothelial cells of intact arteries to release NO and possibly a hyperpolarizing factor, (3) EFS of BAEC causes release of NO, and (4) EFS-induced relaxation depends on vascular smooth muscle cell membrane repolarization and endothelial cell release of vasoactive substances.

Animals

Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone Japanese quail.

The purpose of this study was to characterize the lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and commercially available (CA) Japanese quail were fed either a semi-purified diet containing 1% cholesterol or a cholesterol-free diet for two weeks. The lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The lipoprotein distribution patterns obtained from both strains showed an HDL-predominant pattern. A protein of 26 kDa was the major apoprotein in the entire density range of the lipoprotein class. Marked increases in the cholesterol ester levels were observed in the lower density fractions (1.006 < d < 1.055: chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46% of the total lipids in CA quail and 54% in HAP quail. In addition, the presence of a protein of 470 kDa was exclusively observed in the lower density fractions (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions of the chylomicron and VLDL fractions were affected by the dietary cholesterol in both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight %). However, cholesterol feeding had no effect on the level of cholesterol, chemical composition or fatty-acid composition of the HDL fractions in either strain. Although the lipoprotein and apoprotein profiles of HAP quail showed resemblances to those of the CA quail, expression of the 470 kDa protein in the lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was discussed in this study.

Animals

Simultaneous bilateral pallidoansotomy for idiopathic dystonia musculorum deformans.

A 17-year-old Russian male with a 9-year diagnosed history of dystonia musculorum deformans manifested as severe tortipelvis, lordosis, and axial and appendicular spastic dystonia, refractory to medical therapy, is reported. This patient underwent a simultaneous bilateral pallidoansotomy with dramatic results. Postoperative evaluation revealed sustained alleviation of all dystonic symptoms and abnormal movements. Rapid recovery of useful strength in all limbs as well as dramatic improvement in coordination occurred. Bilateral posteroventral pallidotomy and pallidoansotomy in the past have proven effective in alleviation of all parkinsonian symptoms, including dyskinesia and dystonia, without the concurrent risk of intransigent side effects associated with bilateral thalamotomy or other stereotactic surgical procedures. Pallidoansotomy may prove to be the treatment of choice for idiopathic torsion dystonia and merits further investigation.

Adolescent

Osteochondroma after total body irradiation in bone marrow transplant recipients: report of two cases.

We present two cases of osteochondroma after total body irradiation in bone marrow recipients, the first in a 6-year-old boy with juvenile chronic myelogenous leukemia and the second in a 13-year-old boy with acute myelogenous leukemia. The patients developed multiple osteochondromas three years and seven years, respectively, after 12 Gy of total body irradiation. Neither had a family history of hereditary multiple osteochondromatosis. A review of the English literature revealed only one report describing five cases of osteochondroma after 12 Gy of total body irradiation in bone marrow transplant recipients. Osteochondroma should be considered as an additional adverse effect of total body irradiation.

Adolescent

Thallium-201 scintigraphy to assess effect of chemotherapy in osteosarcoma.

UNLABELLED: Imaging results in patients with high-grade osteosarcoma of the extremities were reviewed to determine whether scintigraphic appearance correlated with histologic response to preoperative chemotherapy. METHODS: Histologically, the percent tumor necrosis in specimens from 30 patients were classified into three grades: grade 1 = necrosis less than 60%, grade 2 = 60%-89% necrosis and grade 3 = diffuse necrosis greater than 90% based upon whole transverse sections. Scintigraphically, we analyzed 201TI uptake before and after preoperative chemotherapy. The changes in the tumor-to-background ratio were defined by an alteration ratio. RESULTS: Of the 11 patients with a grade 1 response, the ratio showed -67.1% +/- 45.4% (mean +/- s.d.). Of the 9 patients with a grade 2 response, the ratio showed 37.9% +/- 29.9% of the 10 patients with a grade 3 response the ratio showed 105.5% +/- 12.4%. The ratios correlated well with the histologic grades (p < 0.0001; analysis of variance). CONCLUSION: Thallium-201 scintigraphy accurately assesses the effect of chemotherapy on osteosarcoma.

Adolescent

Chronic anterior pallidal stimulation for Parkinson's disease.

We present the case of a 51-year-old female who had a four-year history of Parkinson's disease with severe "on-off' and disabling progression of symptoms on chronic levodopa therapy. After obtaining FDA approval, we implanted a Medtronic deep brain stimulation lead stereotactically into the right anterior pallidum contralateral to her most symptomatologic side. Intra-operative stimulation trials at 100 Hz caused reproducible reversal of akinetic symptoms and simultaneous microelectrode recording of the posteroventral pallidum revealed decreased neural activity during anterior pallidal stimulation. The patient was evaluated pre-operatively and postoperatively using the Hoehn and Yahr Staging Scale, the Unified Parkinson's Disease Rating Scale (UPDRS), videotape, and a computerized data glove. Six months after implantation, the total UPDRS score was decreased from 68 to 8 and Hoehn and Yahr Staging improved from 3.0 to 1.5 during periods of chronic high frequency stimulation. Dramatic improvements in tremor, dystonia, bradykinesia, and akinesia were noted within seconds of stimulator activation and were also objectively measured using a computerized data glove. This case reveals the potential for therapeutic pallidal stimulation for Parkinson's akinetic symptomatology.

Antiparkinson Agents

The results, indications, and physiology of posteroventral pallidotomy for patients with Parkinson's disease.

In the past, stereotactic surgical intervention for Parkinson's disease was considered indicated only in those patients with active motor manifestations that were refractory to pharmacological therapy, manifestations such as tremor, rigidity, dystonia, and dyskinesia. With the reintroduction and refinement of Leksell's posteroventral pallidotomy, both akinetic and hyperkinetic symptoms are now amenable to surgical treatment. We have analyzed the results of 126 patients who underwent either unilateral (n = 58) or bilateral (n = 68) posteroventral pallidotomies. The Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Staging Scale were used for preoperative and postoperative objective assessments. Postoperative follow-up evaluation occurred initially at 1 week and subsequently at intervals between 1 and 12 months (mean = 4.5 months) after surgery. Although individual motor subscores on the Unified Parkinson's Disease Rating Scale were significantly reduced (n = 126, P < or = 0.01), the most dramatic findings were the reversal of akinetic symptoms and the elimination of dyskinesia and profound "off" periods. These clinical results, combined with intraoperative microelectrode records revealing pallidal neuronal hyperactivity, suggest a reconsideration of the pathophysiology of akinesia and point to possible mechanisms of akinesia improvement by posteroventral pallidotomy in some parkinsonian subgroups.

Adult

EEG frequency patterns in the cat prepyriform cortex during sleep and waking.

The cellular populations in the prepyriform cortex are a primary processing station for sensory information from the olfactory bulb. These populations are also influenced from forebrain and other brain systems involved in behaviour. Recording electrodes can be precisely placed in this cortex compared to many other brain structures. This permits straddling the cortical superficial pyramidal cell layer with a bipolar recording configuration and the ability to obtain information about awake-vigilant and other state conditions from this brain structure. Methadone, a vigorously arousing drug in the cat, and a short acting barbiturate was administered to compare the differences of EEG patterns obtained during normal awake and sleep conditions. Fourier analysis was used in this study and combined with computer profiles of spectra to show time relationships of the state conditions in the cortex. Good separation of the spectra, between the major states in the cat, were observed using this technique for both natural and drug-induced changes.

Animals

The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat.

The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to peduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 +/- 0.53 microns. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Cross-sectional area measurements of the LOT were obtained from tissue prepared for light microscopy. The area decreased from about 0.3 to 0.2 mm2 across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT to mathematically reconstruct action potentials. The empirically derived mono- and biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.

Action Potentials

Oxidative metabolism during and following ischemia of cat spinal cord.

Spinal cord ischemia was produced by an occlusion of the thoracic descending aorta on experimental cats for the periods of 3, 5, 10, and 15 minutes. The reduction/oxidation (redox) ratio of cytochrome a,a3 was measured in vivo by reflectance spectrophotometry, simultaneously with the measurement of the following: blood pressure in the aorta distal to the occlusion; relative blood volume in the cord; oxygen tension in cord tissue; and cord potential in response to dorsal root stimulation. During aortic occlusion, the maximum increase in the redox ratio was reached somewhat more slowly than the maximum decrease in blood pressure, blood volume, and oxygen tension. Interneuron potentials began to decrease as the redox level increased, and completely disappeared soon after the redox ratio increased, and completely disappeared soon after the redox ratio increased maximally. During ischemia, therefore, oxygen consumption in the mitochondria was slightly lower than the decrease in oxygen tension; impairment of ADP phosphorylation, and accordingly that of ion pump, occurs simultaneously with the increase in the redox ratio. Recovery of the redox ratio after completion of aortic occlusion was also slightly slower than the recovery of blood pressure, blood volume, and oxygen tension. Complete recovery of interneuron potentials was much more delayed than that of the redox ratio; after 15-minute ischemia, uncoupling of ADP phosphorylation was noted. It can be concluded that the spinal cord function and metabolism are severely impaired after 15-minute occlusion.

Adenosine Diphosphate