[Case of symptomatic epilepsy presenting with focal high intensity on diffusion-weighted image prior to initial convulsive seizure].

It has been reported that high intensity on diffusion-weighted image (DWI) in magnetic reasonance imaging (MRI) accompanying a reduction of the apparent diffusion coefficient (ADC) can be detected at the ictal or postictal stage of epileptic seizure. However, it remains unclear whether such a change results from persisting systemic convulsive seizure or from certain physiological changes such as recurrent epileptic discharge prior to the occurrence of obvious convulsion. We report here a case of symptomatic epilepsy displaying a high intensity area on DWI in MRI before convulsive seizure was initiated. A 64-year-old man was admitted to our hospital due to complaints of dizziness and motor weakness. CT and conventional MRI scans failed to reveal any new lesions except for the scar of a ventricular tube in the right parietal lobe, which had been removed due to shunt infection. The DWI, however, demonstrated an apparent high intensity in the right parietal cortex, and the ADC was significantly reduced as compared to that on the contralateral side. Five days after admission, the patient showed convulsive seizures beginning from the right face and upper extremity which subsequently developed to status epilepticus. Following recovery from the convulsions with administration of anticonvulsants, the high intensity of the right parietal lobe on DWI appeared to be diminished. The present case indicates that the manifestation of a high intensity on DWI concomitant with ADC reduction at the epileptic focus can be readily induced by the occurrence of epileptic discharges before convulsive seizure is evident.

[Monostotic fibrous dysplasia of the cranial vault: a case report].

Fibrous dysplasia, when it occurs in the craniofacial region, mostly involves the skull base and is rarely localized in the cranial vault. Although there have been several reports on magnetic resonance imaging (MRI) findings of fibrous dysplasia involving the skull base, cases occurring in the cranial vault have seldom been reported. We describe here a rare case of monostotic fibrous dysplasia that occurred in the parietal bone and discuss the characteristics of the MRI findings. A 47-year-old female was admitted to our hospital with a complaint of vertigo. A computed tomography (CT) scan did not reveal any intraparenchymal lesions in either the infra- or supratentorium, and her vertigo improved immediately without any treatments. However, a solitary osteolytic lesion was found incidentally in the left parietal bone. MRI showed that the lesion demonstrated hypointensity on T1-weighted images and hyperintensity on T2-weighted images, and was enhanced heterogeneously following injection of Gadolinium-DTPA. Removal of the parietal bone containing the lesion was performed according to the patient's wishes. The histopathological findings of the removed tissues corresponded to fibrous dysplasia. Although it is well known that craniofacial fibrous dysplasia demonstrates iso- or hypointensity on T1- as well as T2-weighted images, in the present case, the lesion showed apparent hyperintensity on T2-weighted images. These findings suggest that fibrous dysplasia can display various MR intensities depending on its origin.

Role of hematopoietic microenvironment in prolonged impairment of B cell regeneration in age-related stromal-cell-impaired SAMP1 mouse: effects of a single dose of 5-fluorouracil.

In this study, we examined the age-associated defect of stromal cells, which support B cell development, treated with 5-fluorouracil (5-FU) to induce severe perturbation of hematopoiesis, including B lymphocyte development, using SAMP1 mice exhibiting senescence-mimicking stromal-cell impairment after 30 weeks of age. Significant findings of this study are as follows: first, a marked and prolonged decrease in number of CFU-preB cells in non-SCI mice (58% of the steady-state level) associated with more markedly depressed number of CFU-preB cells in SCI mice (20% of the steady-state level), despite the absence of difference in the number of CFU-GMs during the period; second, in the non-SCI mice, a significant and prolonged up-regulation of GM-CSF and IL-6, positive regulators of myelopoiesis and suppressive factors of B lymphopoiesis, was observed. In SCI mice, greater and prolonged suppression of B lymphopoiesis was clearly demonstrated by the significant up-regulation of the negative regulator TNF-alpha associated with the concomitant marked down-regulation of the positive regulator SDF-1, although the increases of GM-CSF and IL-6 were limited. That is, 'negative complementation' makes preB recovery after 5-FU treatment impaired and prolonged. Principal component analysis clearly showed differences in the cytokine expression patterns in both early and later phases and the time course of the expression pattern of each cytokine between SCI and non-SCI mice without supervising information. An impaired regulation of the expressions of not only positive but also negative regulators after 5-FU treatment was, in part, the cause of the impaired regeneration of CFU-preB cells in SCI mice.

Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury.

OBJECTIVE: Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses. METHODS: EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes). RESULTS: Ten minutes after injury, microglial activation with increased OX42 immuno-reactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions. DISCUSSION: These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.

Jugular bulb venous thrombosis caused by mild head injury: a case report.

BACKGROUND: We present here the first report of a jugular bulb venous thrombosis after mild head injury, which lacked either a skull fracture or abnormal findings on CT scan. CASE DESCRIPTION: An 8-year-old boy was hit on the back of the head and experienced headache and vomiting beginning the next morning. A CT scan and cranial x-ray examination failed to reveal any abnormal findings. The patient was treated conservatively; however, his headache and vomiting persisted. At 13 days after the injury, he began to show double vision due to left VIth nerve palsy and bilateral papilloedemas, suggesting an increased ICP. Although repeated CT scan failed to detect abnormal findings in both the supra- and infra-tentorial regions, MRI clearly visualized a thrombus which was situated within the right jugular bulb. Furthermore, MRV demonstrated disruption of venous flow at the jugular bulb. The patient was administered heparin continuously. His symptoms improved and the CSF pressure on lumbar puncture returned to a normal level at 20 days after admission. Magnetic resonance imaging showed resolution of the clot, and MRV appeared to demonstrate partial recanalization simultaneously. The patient was discharged without any neurologic deficits. The clot in the jugular bulb disappeared completely after 4 months, and he could be followed up for 1 year. CONCLUSION: This case underscores the fact that MRI may represent the exclusive screening examination in cases of sinus thrombosis when it occurs within the jugular bulb, as CT scan fails to reveal any findings suggestive of venous thrombosis.

Inflammatory biomarker, neopterin, suppresses B lymphopoiesis for possible facilitation of granulocyte responses, which is severely altered in age-related stromal-cell-impaired mice, SCI/SAM.

Neopterin is produced by monocytes and is a useful biomarker of inflammatory activation. We found that neopterin enhanced in vivo and in vitro granulopoiesis triggered by the stromal-cell production of cytokines in mice. The effects of neopterin on B lymphopoiesis during the enhancement of granulopoiesis were determined using the mouse model of senescent stromal-cell impairment (SCI), a subline of senescence-accelerated mice (SAM). In non-SCI mice (a less senescent stage of SCI mice), treatment with neopterin decreased the number of colonies, on a semisolid medium, of colony-forming units of pre-B-cell progenitors (CFU-preB) from unfractionated bone marrow (BM) cells, but not that from a population rich in pro-B and pre-B cells without stromal cells. Neopterin upregulated the expression of genes for the negative regulators of B lymphopoiesis such as tumor necrosis factor-alpha (TNF-alpha ), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in cultured stromal cells, implying that neopterin suppressed the CFU-preB colony formation by inducing negative regulators from stromal cells. The intraperitoneal injection of neopterin into non-SCI mice resulted in a marked decrease in the number of femoral CFU-preB within 1 day, along with increases in TNF-alpha and IL-6 expression levels. However, in SCI mice, in vivo and in vitro responses to B lymphopoiesis and the upregulation of cytokines after neopterin treatment were less marked than those in non-SCI mice. These results suggest that neopterin predominantly suppressed lymphopoiesis by inducing the production of negative regulators of B lymphopoiesis by stromal cells, resulting in the selective suppression of in vivo B lymphopoiesis. These results also suggest that neopterin facilitated granulopoiesis in BM by suppressing B lymphopoiesis, thereby contributing to the potentiation of the inflammatory process; interestingly, such neopterin function became impaired during senescence because of attenuated stromal-cell function, resulting in the downmodulation of the host-defense mechanism in the aged.

[A case of nasal dermal sinus-cyst (NDSC) with intracranial extension].

Nasal dermal sinus-cyst (NDSC) is a rare abnormality consisting of a dermal sinus opening at the nasal skin and dermoid cyst localized in the frontobasal area. A 2-year-old boy was admitted to our hospital due to swelling of the fronto-nasal regions with pus running from an orifice situated in the nasal skin. Bone-image CT and 3D-CT revealed bone defects within the frontal skull base. MRI demonstrated that a dermoid cyst centered in a bone defect was in contact with the dura of the frontobasal area, and a dermal sinus extending to the frontonasal skin could also be detected. Surgical resection was performed by frontobasal craniotomy. The dermal sinus was followed subcutaneously into the orifice of the nasal skin. A small skin incision was made and the sinus was then totally removed. The authors describe in detail this case of NDSC which extended to the intracranium, and review the literature regarding this abnormality.

Inflammatory biomarker, neopterin, enlarges splenic mast-cell-progenitor pool: prominent impairment of responses in age-related stromal cell-impairment mouse SCI/SAM.

Neopterin is produced by monocytes and is a useful biomarker of inflammatory responses. We found that neopterin enhances granulopoiesis, but suppresses B-lymphopoiesis triggered by the positive and negative regulations of cytokines produced by stromal cells in mice. In this study, neopterin was found to regulate mast cell development, which was confirmed in the mouse model of senescent stromal-cell impairment (SCI). In non-SCI mice (=less senescent stage of SCI mice), neopterin decreased the number of colonies of IL-3-dependent mast-cell progenitor cells (CFU-mast) from unfractionated bone-marrow cells, but not that from the lineage-negative bone-marrow cell population without stromal cells in a semisolid in vitro system. Neopterin increased the gene expression and protein production of TGF-beta, a negative regulator of CFU-mast, in cultured stromal cells, indicating that neopterin suppressed CFU-mast colony formation by inducing TGF-beta in stromal cells. In contrast to this in vitro study, in vivo treatment with neopterin did not significantly up-regulate TGF-beta. The intravenous injection of neopterin into mice decreased the number of femoral CFU-mast and the expression level of the gene for stem cell factor (SCF), a positive regulator of CFU-mast, whereas the number of splenic CFU-mast and SCF gene expression level increased. In SCI mice, the in vivo and in vitro responses of mast cell development and cytokine gene expression level to neopterin treatment were less marked than those in non-SCI mice. These results suggest that, firstly, neopterin augments the splenic pool of CFU-mast by the production of SCF, and secondly, such neopterin function becomes impaired during senescence because of an impaired stromal-cell function, resulting in the down-modulation of host-defense mechanisms.

[Superior sagittal sinus thrombosis suffered as a complication of ulcerative colitis: case report].

A case of superior sagittal sinus thrombosis which was complicated with ulcerative colitis is reported. A 16-year-old male patient had a 2-year history of ulcerative colitis. He was admitted to our hospital complaining of abdominal pain, bloody bowel discharge and appetite loss, and was then treated conservatively. Two days after admission, he demonstrated generalized convulsions which were followed by right hemiplegia. MRI showed a low intensity lesion on T1 and an irregular high intensity in the subcortical area of the left frontal lobe on T2 and T2 FLAIR-weighted images. The MRI findings resembled either invasive brain tumor or local inflammation. Cerebral angiography appeared to demonstrate complete obstruction of the superior sagittal sinus with congestion of venous flow in the cortical veins. Ulcerative colitis has been reported to show hypercoagulation, leading to deep vein thrombosis within the body which sometimes causes pulmonary infarction; however, occurrence of venous thrombosis in the intracranial veins and sinus is rare. This report underscores the fact that cerebral venous thrombosis should be suspected in the case of patients with ulceritive colitis who suffer sudden onset of neurological deficits.

Effects of neopterin on the hematopoietic microenvironment of senescence-accelerated mice (SAM).

The pteridine neopterin (NP) is produced by monocytes and is known to be a useful marker of immunological activation, although, it remains elusive whether neopterin itself exhibits biological functions. Recently, we found that NP stimulates hematopoietic cell proliferation and differentiation by activating bone marrow stromal cell function. In order to elucidate the biological effect of NP on stromal cells, its effects on hematopoiesis was determined in the mouse model of age-related stromal impairment, senescence-accelerated mice (SAMs). An intraperitoneal administration of NP increased the number of peripheral leukocytes and CFU-GM in the bone marrow and spleen of young SAMs, however, no increase of CFU-GM in old SAMs (stromal impairment) was observed when compared with young SAMs. NP also increased the CFU-GM colony formation of bone marrow and spleen cells from young SAMs in a soft agar culture system, but it did not enhance CFU-GM colony formation of cells from old SAMs cultured in this system. Treatment with NP induced the production of hematopoietic stimulating factors, including IL-6 and GM-CSF, by bone marrow stromal cells from young SAMs but stromal cells from old SAMs did not respond to NP stimulation. Further studies will be required to clarify the mechanism by which NP stimulates the production of hematopoietic growth factors from stromal cells, the results of this study indicate that NP is a potent hematopoietic regulatory factor by activating stromal cell function(s).

Tissue plasminogen activator extravasated through the cerebral vessels: evaluation using a rat thromboembolic stroke model.

Neurotoxic effects of endogenous tissue plasminogen activator (tPA) have recently been reported. Employing a rat model of thromboembolic stroke, we evaluated the extent and degree of extravasation of exogenous tPA administered for the purpose of fibrinolysis. In a thromboembolic model using Sprague-Dawley rats, focal cerebral ischemia was induced at the territory of the middle cerebral artery (MCA). Early reperfusion was induced by administering tPA (10 mg/kg) intravenously at 30 minutes after the onset of ischemia. Extravasated tPA was evaluated by immunohistochemistry, and the concentration of tPA in the brain tissue was quantified by enzyme-linked immunosorbent assay methods. The integrity of the blood-brain barrier (BBB) was examined electronmicroscopically. In a thread model of transient ischemia, reperfusion was induced without tPA administration at 30 minutes or 2 hours after the onset of ischemia, and the tPA content of the brain was quantified. In the rats with thromboembolic stroke, extravasation of tPA was observed at the territory of the MCA. Both the endogenous and exogenous tPA contents were 3.5 +/- 1.6 ng/ml of homogenized brain in saline. Electronmicroscopically, mild ischemic changes were observed, although the integrity of the BBB was preserved. In the thread model rats, the endogenous tPA contents of the ischemic hemisphere were 0.9 +/- 0.1 and 1.0 +/- 0.2 ng/ml in the 30-minute and 2-hour ischemia groups, respectively, and were significantly lower than the tPA contents in the thromboembolic stroke rats (p<0.01). The present findings indicate that significant extravasation of exogenous tPA occurs through the cerebral vessels even though early reperfusion is induced.

Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.

A novel supramolecular oligomer, cyclic polylactate (CPL) that was originally discovered in the culture medium of HeLa-S tumor cells, reportedly inhibits the growth of FM3A ascites tumor cells by inhibiting enzymes involved in the glycolytic pathway. We synthesized CPL containing 3- to 13-mers by prolonged heating and rapidly mixing a carbohydrate compound of the L-lactic acid monomer (C(3)H(6)O(3)) under decreased pressure, and studied its effects on the growth of the cloned leukemic cell, TF-1. CPL inhibited the growth of TF-1 cells and induced 7A6 antigen, which is expressed by cells undergoing apoptosis, on the surface of TF-1 cells. In addition, caspase 3, 8 and 9 activities of TF-1 cells were increased after exposure to CPL, indicating that CPL induces apoptotic changes in TF-1. Among the 6 glycolytic enzymes examined in this study, the activities of PFK and HK, induced by CPL, decreased. Interestingly, CPL was detected in conditioned medium of the stromal cell line, LS801, obtained from human bone marrow. This conditioned medium inhibited the growth of TF-1 cells, and induced the expression of 7A6 antigen. These findings suggest that CPL will be a useful chemotherapeutic agent against leukemia.