Hisao Koga

Effects of interleukin-1 and arachiodonate on the preoptic and anterior hypothalamic neurons

Effects of microelectrophoretic application of ultrapure human interleukin-1 (IL-1), an endogenous pyrogen, on the activity of 80 neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in the urethane anesthetized rat. IL-1 predominantly decreased the activity of warm-sensitive neurons (15 of 19) and increased the activity of cold-sensitive neurons (10 of 12), but had no effect on 37 of 49 thermally insensitive neurons. The neuronal responses to IL-1 were blocked or attenuated by concurrent application of mepacrine (a phospholipase inhibitor) or sodium salicylate (a cyclooxygenase inhibitor). Local application of sodium arachidonate decreased the activity in 17 of 28 warm-units and excited 12 of 16 cold-units, and the effects of arachidonate were blocked by sodium salicylate. The results are compatible with the view that one or more cyclooxygenase metabolites of arachidonic acid are involved in the IL-1 induced fever.

Convergence of thermal, osmotic and cardiovascular signals on preoptic and anterior hypothalamic neurons in the rat

Responsiveness of thermosensitive neurons in the preoptic and anterior hypothalamus (PO/AH) to osmotic and cardiovascular signals have been shown to be responsible, at least partly, for the reduced thermoregulation during dehydration and the hypothermia after acute blood loss. The responsiveness to local and peripheral (hepatoportal) osmotic stimuli were found in about 60% of PO/AH thermosensitive neurons and 12% of thermally insensitive neurons in tissue slices in vitro and in urethane-anesthetized rats. Since hyperosmotic stimuli predominantly decreased the activity of both warm-sensitive and cold-sensitive neurons, the reduced heat loss and heat production during dehydration may be explained by altered activity of PO/AH thermosensitive neurons induced by hyperosmolality. About 42% of 250 PO/AH neurons (66.3% of thermosensitive neurons and 30% of thermally insensitive neurons) exhibited the responsiveness to changes in blood pressure by less than 15 mmHg, which was found to be mediated by baro/volume receptors. Hypotensive stimuli predominantly increased the activity of warm-sensitive neurons and decreased the activity of cold-sensitive neurons. The neuronal responses may explain, at least in part, the hypothermia after acute bleeding.

Dysembryoplastic neuroepithelial tumor: Report of three cases

BACKGROUND Dysembryoplastic neuroepithelial tumor (DNT) is one of the mixed neuronal-glial tumors that should be differentiated from low-grade gliomas. The recognition and correct diagnosis of DNT is important because this tumor is curable by excision. METHODS We report three cases of histologically proven DNTs with various image studies performed preoperatively and describe characteristic findings of them, as well as those of previous reports. RESULTS In our three cases, computed tomography (CT) showed a well-defined, nonenhancing hypodense area. Magnetic resonance imaging (MRI) demonstrated a cortical mass of hypointensity on T1- and of marked hyperintensity on T2-weighted images. I-123-IMP or Tc-99m-HMPAO single-photon emission computed tomography (SPECT) images showed marked hypoperfusion of the lesion. Thallium-SPECT showed no uptake. CONCLUSIONS I-123-IMP, Tc-99m-HMPAO, and Thallium-SPECT images, as well as CT and MRI, may be helpful in distinguishing DNT from low-grade gliomas.

Responses of anterior hypothalamic-preoptic thermosensitive neurons to thyrotropin releasing hormone and cyclo(his-pro)

Effects of local application of thyrotropin releasing hormone (TRH) and its metabolite, histidyl-proline diketopiperazine [cyclo (His-Pro)], on the activity of thermosensitive and thermally-insensitive neurons of the anterior hypothalamic-preoptic area were investigated in urethane-anesthetized rats. Microelectrophoretic application of TRH changed the activity of 126 of 206 neurons tested. Thyrotropin releasing hormone predominantly decreased the activity of warm-sensitive neurons and increased the activity of cold-sensitive neurons. Since it has been generally assumed that warm-sensitive and cold-sensitive neurons in the anterior hypothalamic-preoptic area mediate heat and cold defence responses, respectively, the present results are consistent with previous findings showing hyperthermia after injection of TRH into the hypothalamus in the rat. Cyclo (His-Pro) affected the activity of 59 of 153 neurons tested. In addition, cyclo (His-Pro) did not preferentially affect warm- or cold-sensitive neurons. These results indicate that the previously-determined hypothermic effect of cyclo (His-Pro) cannot be explained by its effects on thermosensitive neurons in the anterior hypothalamic-preoptic area.

Responses of preoptic thermosensitive neurons to changes in blood pressure

Effects of changes in arterial blood pressure were studied on the neuronal activity of 56 thermosensitive and 122 thermally insensitive neurons of the preoptic and anterior hypothalamus (PO/AH) in the urethane-anesthetized rat. Falls in blood pressure by 15 mmHg or less, which were induced by hemorrhage or by IV injection of vasoactive drug, resulted in the increased activity of warm-sensitive neurons (53.3%) and the decreased activity of cold-sensitive neurons (45.5%). However, the majority (71.3%) of thermally insensitive neurons were not affected by a rise or a fall in blood pressure by as large as 30 mmHg. Bilateral sections of glossopharyngeal, vagus and sympathetic nerves abolished the neuronal responses to blood pressure changes, indicating that the responses are mediated largely by peripheral baro/volume receptors. Increased and decreased activities of warm-sensitive neurons and cold-sensitive neurons during hypotension respectively suggest that at least a part of hypothermia observed during acute hemorrhage is a centrally induced response having a survival value.

Apparent diffusion coefficient (ADC) and magnetization transfer contrast (MTC) mapping of experimental brain tumor.

Brain tumor tissue contains different pathological areas, such as tumor cell rich parts, necrotic tissues, and cyst. Furthermore, both neovascularization and edema formation progress along with the tumor progression. In this study we employed diffusion weighted (DW) and magnetization transfer contrast (MTC) imaging to chronologically investigate the biological characteristics of a rat glioma. RG-2 glioma cells were implanted stereotactically into the right hemisphere of male Wistar rats. MR images were taken 1, 2 and 3 weeks after inoculation. Apparent diffusion coefficient (ADC) and MTC values were calculated as follows; ADC = -ln (SI-DW/SI-T2)/1096, MTC = 1-SI-MTon/SI-MToff. Each mapping image was made based on the calculated average values of four pixels. The spatial signal changes and the real values were compared to the histological findings. The apparent increase of ADC was noted in the parenchyma adjacent to tumor suggesting the progression of edema. The tumor itself had similar or slightly increased ADC. Cystic and necrotic components appeared 2 weeks after implantation and they showed significantly higher ADC than those calculated in the contralateral putamen. On the other hand, MTC was slightly decreased in the parenchyma adjacent to the tumor, markedly within the tumor, and maximally in the cystic and necrotic area suggesting accumulation of macromolecules such as growth factors, cytokines, and serum albumin.

Convergence of hepatoportal osmotic and cardiovascular signals on preoptic thermosensitive neurons.

Effects of hepatoportal osmotic stimuli and changes in arterial blood pressure were studied on the neuronal activity of 24 thermosensitive and 47 thermally insensitive neurons of the preoptic and anterior hypothalamus (PO/AH) in the urethane-anesthetized rat. Infusion of hypertonic (3% NaCl, 9% mannitol) or hypotonic (water) solutions into the hepatic portal vein changes the activity in 59% of thermosensitive neurons and 13% of thermally insensitive neurons but the injection into the femoral vein did not. Changes in blood pressure induced by intravenous injection of vasoactive drugs altered the activity of thermosensitive neurons (75%) and thermally insensitive neurons (32%). Neurons having dual sensitivity to both osmotic and blood pressure were more frequently found among thermosensitive neurons (10/24) than among thermally insensitive neurons (4/47), chi 2(1) = 11.03, p less than 0.001. The convergence of osmotic and baro/volaemic information on thermosensitive neurons may provide explanations for thermoregulatory changes observed during dehydration and acute hypotension.

A possible clinical application of multicytokine-producing cytotoxic mononuclear cell (MCCM) therapy

When peripheral blood mononuclear cells (PBMC) were incubated with a streptococcal preparation, OK-432, for 24 h, PBMC acquired cytolytic activity against cultured and fresh human tumor cells. Such PBMC were called OK-432-activated mononuclear cells (OK-MC). OK-MC produce several kinds of cytokines such as interferonα (IFNα), IFNγ, and tumor growth inhibitory factor (TGIF) bothin vitro andin vivo. OK-MC-produced cytokines also inhibited the growth of cultured and fresh human tumor cells. The growth inhibition was examined by human tumor clonogenic assay using a double-layer agar technique. The results indicate that two pathways of anti-tumor activity are induced in OK-MC, i.e., cell-mediated and cytokine-mediated.

Solitary spinal epidural cavernous haemangioma presenting as acute epidural haematoma.

This report describes a case of solitary spinal epidural cavernous haemangioma presenting as an acute epiduralhaematoma. The patient is a 50 year old diabetic female with right brachalgia and hemiparesis. Magnetic resonance imaging (MRI) demonstrated the presence of a cervical spinal epidural haematoma. The patient underwent laminectomy and total removal of the haematoma and the accompanying vascular tissue. The diagnosis of cavernous haernangioma was proven by histological examination. Because the source of bleeding in most cases of spontaneous spinal epidural haematoma is usually obscure, the authors emphasise the possibility that a small cavernous haemangioma can be one of the bleeding sources in some of these cases.