Yoshimasa Kinoshita

Proton magnetic resonance spectroscopy of brain tumors: an in vitro study.

The ability of proton magnetic resonance spectroscopy (1H MRS) to diagnose brain tumors was investigated using in vitro high-resolution spectra. Fifty-eight surgically excised samples of brain tumors (12 glioblastomas, 4 anaplastic astrocytomas, 6 astrocytomas, 12 meningiomas, 6 neurinomas, 4 chordomas, 3 craniopharyngiomas, 2 pituitary adenomas, 2 malignant lymphomas, 1 ependymoma, 1 medulloblastoma, and metastatic brain tumors including 3 pulmonary adenocarcinomas, a hepatocellular carcinoma, and a renal cell carcinoma) and 4 nontumorous lobectomized brains were examined by in vitro 1H MRS. N-Acetyl-aspartate was demonstrated in normal tissues but could not be detected in nonneuroectodermal tumors. Total creatine was decreased in all brain tumors in comparison with normal brain tissues, but was relatively higher in neuroectodermal tumors than in other brain tumors. Choline-containing compounds were present in all tumors except craniopharyngioma, and their concentrations were particularly high in a metastatic brain tumor from hepatocellular carcinoma. The concentration of glycine was high in neuroectodermal tumors, whereas that of taurine was high in medulloblastoma, pituitary adenoma, and renal cell carcinoma. Alanine was increased in meningioma, glioma, and pituitary adenoma. Neurinoma had the largest inositol content among the tumors examined. Thus each type of brain tumor exhibited a characteristic MR spectrum. These data suggested that in vivo 1H MRS might provide clinically useful information about tumor metabolism and aid in the differential diagnosis of tumors. Although excellent anatomical localization of tumors can be readily obtained by MR imaging, MRS may provide additional information in cases in which the differential diagnosis of tumors by MR imaging is difficult.

THE EXPRESSION OF TUMOR NECROSIS FACTOR-ALPHA IN THE RAT BRAIN AFTER FLUID PERCUSSIVE INJURY

Abstract To investigate the role of tumor necrosis factor-α (TNFα) after traumatic head injury in rats, moderate brain injury of 1000 mmHg was generated by an original fluid percussion injury device. TNFα levels in cerebrospinal fluid (CSF) gradually increased during the first 1 h, rose to a maximal elevation at 3 h and 6 h and returned to basal values by 24 h. Horseradish peroxidase tracer experiments revealed that primary microvascular damage appeared as early as 15 min after impact, but rapidly recovered and 1 h after impact secondary microvascular damage occurred in the hippocampus and parasagittal cortex. By immunoelectron microscopy, TNFα reactions were detected in the lysosomes of microglia accumulated at the impact site of the cortex 30 min after impact, and 1 h after impact these reactions were mainly detected at the glial cells (such as microglia and astrocytes) in the hippocampus and parasagittal cortex. Therefore the delayed microvascular damage observed in sites remote from the impact may be induced by TNFα which is synthesized mainly by glial cells. The present study suggests that TNFα conveyed from the microglial cells is one cofactor contributing to the fluid percussive brain edema formation after moderate brain injury.

The expression of tumour necrosis factor in the hypothalamus after treatment with lipopolysaccharide

To investigate the effects of tumour necrosis factor (TNF) in the hypothalamus, Wistar rats received an intravenous administration of lipopolysaccharide (LPS) at a dose of 3.0 mg/100 g. Concentrations of TNF‐α in the cerebral liquor and blood sera rapidly increased at 30 minutes after administration of LPS, rose to the maximum level at 1 hour, and then gradually decreased. Using horse‐radish peroxidase as a tracer, a transient increase in paracellular permeability throughout the tight junctions of the ependymal cell layer covering the third ventricle was observed by electron microscopy at 30 minutes and in that of the capillary endothelium at 1 hour after administration, respectively. Following LPS administration, TNF was preferentially localized by immunoelectron microscopy in the tight junctional area of the ependymal cell layer and the capillary. These data indicate that TNF, synthesized in the ependymal cell layer, induces a deterioration in the cerebrospinal fluid–brain barrier and subsequently in the blood–brain barrier. The present study suggests that oedematous changes in the hypothalamic areas determined by ultrastructural and magnetic resonance analyses were mainly due to TNF conveyed from the ependymal cell layer to the hypothalamus after administration of LPS.

The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.

Abstract The immunolocalization of tumor necrosis factor-α (TNFα) after diffuse axonal injury (DAI) is demonstrated using a midline fluid percussion rat model (moderate brain injury of 1000 mm Hg was generated) and the effects of TNFα on the axolemmal permeability using horseradish peroxidase as a tracer. In addition, the accumulation of β-amyloid precursor protein (β-APP) was investigated, which has recently been shown to be a reliable marker for the diagnosis of DAI in cases with fatal head injury. TNFα levels in brain tissues from the impact site and the cortex including the corpus callosum, gradually increased during the first 1 h, rose to a maximal elevation at 3 h, gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15 min after impact but rapidly recovered and that 1 h after impact, secondary axonal damage occurred in the corpus callosum and the brain stem. By immunoelectron microscopy it was seen that β-APP accumulated in the axon from 1 h after impact demonstrating that there was functional axonal damage. TNFα reactions were detected in the lysosomes of microglia 30 min after impact and 1 h after impact these reactions were mainly detected in the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is generally accepted that TNFα directly induces primary demyelination and oligodendrocyte apoptosis. Therefore, TNFα conveyed from the microglial cells is one cofactor contributing to the formation of the delayed axonal damage observed at these sites. The present study suggests that TNFα conveyed from the glial cells may contribute to the pathogenic mechanism of DAI formation following fluid percussive brain injury.

Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.

The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.

Toxicity of Shiga Toxin 1 in the Central Nervous System of Rabbits

ABSTRACT The action of Shiga toxin (Stx) on the central nervous system was examined in rabbits. Intravenous Stx1 was 44 times more lethal than Stx2 and acted more rapidly than Stx2. However, Stx1 accumulated more slowly in the cerebrospinal fluid than did Stx2. Magnetic resonance imaging demonstrated a predominance of Stx1-dependent lesions in the spinal cord. Pretreatment of the animals with anti-Stx1 antiserum intravenously completely protected against both development of brain lesions and mortality.

Brainstem mechanisms of autonomic dysfunction in encephalopathy‐associated Shiga toxin 2 intoxication

Acute encephalopathy is the major determinant of death in an early stage of Shiga toxin (Stx)‐producing Escherichia coli infection. Rapid progress toward refractory hypotension and dysfunction of breathing implies autonomic center dysfunction of patients. To clarify whether autonomic dysfunction becomes an ultimate cause of death in Shiga toxemia, we injected purified Stx2 (20 μg/kg) intravenously into rabbits, and monitored changes in cardiovascular and respiratory function together with renal sympathetic nerve activity (RSNA) in the conscious state. After an approximately 24‐hour silent (lag) period, all rabbits given Stx2 developed hemorrhagic diarrhea (25.7 ± 1.1 hours) and limb paralysis (31.2 ± 1.3 hours). This limb paralysis was observed initially in the hind legs, and then it gradually extended to the forelegs. After 23.2 ± 2.3 hours, RSNA increased gradually, and arterial blood pressure was maintained within normal limits together with an increase in the maximum gain of baroreflex response. Severe hypotension developed within 34.8 ± 2.2 hours, without any increase in heart rate; RSNA significantly increased by 39.5 ± 0.9 hours. In the final stage, RSNA decreased concurrently with decreases in arterial blood pressure, heart rate, and baroreflex response, suggesting dysfunction of the baroreflex control system. Thereafter, all rabbits died within 47.8 ± 1.2 hours after the intravenous Stx2 injection. Magnetic resonance imagings of the central nervous system (T2‐weighted images) showed high‐intensity areas in the dorsal two‐thirds of the cervical spinal cord and brainstem 48 hours after Stx2 administration. These results show that the cause of death is circulatory failure caused by impairment of the cardiovascular center in the medulla. We believe that this animal model helps to clarify the mechanism of rapid progress to death of patients with Shiga toxin–producing E coli infection. Ann Neurol 1999;45:716–723

Successful steroid pulse therapy for brain lesion caused by Shiga toxin 2 in rabbits

Betamethasone sodium phosphate (BSP) is usually used as a steroid therapy for human brain edema. High doses of BSP (36mg/kg) twice a day for two days statistically reduced the mortality rate and improved the survival period of Stx2 (1.4mug/kg; 1.6LD(50))-toxemic rabbits. We made evaluations on three kinds of magnetic resonance images (MRI) including T1-weighted, T2-weighted, and enhanced MRI using gadopentetate dimeglumine (Gd-DTPA) to detect brain lesion induced by an intravenous injection of Stx2 in rabbits. Enhanced T1-weighted MRI was the most sensitive tool to find leakage of Gd-DTPA suggesting impairment of the blood brain barrier caused by Stx2. Enhanced MRI revealed that BSP treatment inhibited the leakage of Gd-DTPA, as directly evidenced by the protective effect of BSP against brain edema induced by intravenous injection of Stx2. Interleukin 1beta was not induced after Stx2 treatment in brain primary mixed cell culture.

Providing Simulation of Medical Manipulation with Haptic Feedback

Accompanying the progress of medical technology, all kinds of treatment and therapy are being practiced in healthcare industry. It is expected that the regional difference in terms of the quality of healthcare in the area of surgery could be reduced through the remote operations with the help of a robot-based surgery system. Such a remote surgery approach, however, is not yet practical, because it solely relies on the visual perception with no input for the haptic perception. Since it is a lot faster for a human being to sense through touching than by watching especially when he is manipulating an object, sensing through touching is considered essential to the success of remote surgery. In this research, a system that is able to sense through a force sensor is developed. The system simulates the process of intracytoplasmic sperm injection (ICSI). PHANToM, a force sensing system, is employed for collecting the information for the haptic perception. With this force sensing system, it is possible to have force input in 6 degrees of freedom and force output in 3 degrees of freedom. OpenGL is used for the 3D graphics rendering in the visual information processing system. By synchronizing the information for both the visual and haptic perception, a virtual reality system that reacts to both the visual and force interactions has been developed. The simulation results reported in this paper proved that using the information collected through the force sensing system makes a significant difference in the medical treatment.

Simulation of ICSI Procedure Using Virtual Haptic Feedback Model

Accompanying the progress of medical technology, all kinds of treatment and therapy are being practiced in healthcare industry. It is expected that the regional difference in terms of the quality of healthcare in the area of surgery could be reduced through the remote operations with the help of a robot-based surgery system. Such a remote surgery approach, however, is not yet practical, because it solely relies on the visual perception with no input for the haptic perception. Since it is a lot faster for a human being to sense through touching than by watching especially when he is manipulating an object, sensing through touching is considered essential to the success of remote surgery. In this research, a system that is able to sense through a force sensor is developed. The system simulates the process of intracytoplasmic sperm injection (ICSI). PHANToM, a force sensing system, is employed for collecting the information for the haptic perception. With this force sensing system, it is possible to have force input in 6 degrees of freedom and force output in 3 degrees of freedom. OpenGL is used for the 3D graphics rendering in the visual information processing system. By synchronizing the information for both the visual and haptic perception, a virtual reality system that reacts to both the visual and force interactions has been developed. The simulation results reported in this paper proved that using the information collected through the force sensing system makes a significant difference in the medical treatment.