Radiation-induced anaplastic ependymoma with a remarkable clinical response to temozolomide: a case report.

Radiation-induced gliomas are uncommon and therapeutic options are limited due to prior exposure to radiotherapy. Meanwhile, the chemotherapeutic response of anaplastic ependymoma, another rare entity in adults, is often disappointing. We report on the first recorded case of radiation-induced anaplastic ependymoma, in which an excellent clinical response to temozolomide was demonstrated.

Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion.

BACKGROUND/AIMS: In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC remain controversial, the morphology and immunohistochemical staining patterns of neoplastic GC cells were compared with those of other gliomas. METHODS: An immunohistochemical analysis of neoplastic cells from four patients with GC and 20 with astrocytic tumours using antibodies against Ki-67, GFAP, and L1, the last of which is a neural cell adhesion molecule putatively related to glioma invasion. RESULTS: GC tumour cells can be divided into two types, those mainly composed of strongly GFAP and L1 positive gemistocytic cells, the other composed of small, GFAP and L1 negative spindle shaped cells. The two types did not differ with respect to Ki-67 positivity. Cells from patients with other gliomas were positive for GFAP but concurrent L1 expression was negative or weakly positive. CONCLUSION: The strong expression of L1 in patients with GC and its poor expression in the 20 patients with other types of glioma, including those with GFAP positive gemistocytic astrocytomas, suggest that L1 expression may play a role in the histogenesis of GC.

Cerebellar glioblastoma genetically defined as a secondary one.

We report here the case of a 29-year-old woman with cerebellar glioblastma. In the present case, tumor lesions were observed in each cerebellar hemisphere. The left-side lesion was diagnosed as glioblastoma, and the right-side lesion as malignant astrocytoma by histopathology. Immunohistochemistry revealed that the tumor cells of the left-side lesion was positive for p53, whereas epidermal growth factor receptors (EGFR) were negative in tumor cells from both sides. Genetic alterations were investigated using a genome DNA microarray (GenoSensor Array 300), which has led us to define this tumor as a secondary glioblastoma. The clinical presentation and genetic findings of this relatively rare entity are discussed.

Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain.

Thermal and mechanical hypersensitivity in the injured region is a common complication. Although it is well known clinically that thermal and mechanical sensitivity of the oral mucosa is different from that of the skin, the mechanisms underlying injured pain of the oral mucosa remain poorly understood. The transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in primary afferent neurons are known to contribute to pathological pain. Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and mechanical hypersensitivity following oral mucosa or whisker pad skin incision. Strong heat and mechanical and cold hypersensitivity was caused in the buccal mucosa and whisker pad skin following incisions. On day 3 after the incisions, the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG) neurons innervating the buccal mucosa and whisker pad skin was significantly increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad skin, but not the buccal mucosa, was significantly increased. Administration of the TRPV1 antagonist, SB366791, to the incised site produced a significant suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin, as well as mechanical allodynia in the whisker pad skin. Administration of the TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as heat hyperalgesia in the whisker pad skin. These findings indicate that altered expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and mechanical hypersensitivity following the buccal mucosa and whisker pad skin incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed TG neurons in whisker pad skin-incised rats may contribute to the intracellular interactions of TRPV1 and TRPA1 associated with whisker pad skin incision, whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal mucosa-incised pain.

Chromosomal aberrations detected by comparative genomic hybridization (CGH) in human astrocytic tumors.

We investigated chromosomal aberrations in 16 patients with astrocytic tumors of various histologic malignancies by comparative genomic hybridization (CGH). The degree of chromosomal loss was shown to be negatively correlated with histologic malignancy. Losses of portions of chromosomes 1p, 19q and 22q were the three chromosomal aberrations observed most frequently. Alterations in multiple chromosomes were observed more frequently in glioblastomas than in astrocytomas or anaplastic astrocytomas (P < 0.001). Primary glioblastomas showed a high frequency of genomic DNA gains (5/7), whereas recurrent glioblastomas from anaplastic astrocytomas did not (0/3). We found CGH to be a powerful tool for surveying DNA alterations in tumors and characterizing the biology of tumors of astrocytic lineage.

Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat.

Aquaporin-4 (AQP4) is a member of a water-selective channel aquaporin-family and mainly expressed in the several structures of the brain and in the collecting duct of the kidney. Here we show its functional involvement in the water homeostasis of the ischemic brain. The expression of AQP4-mRNA is increased in the peri-infarcted cortex during the observation period ( approximately 7 days) after MCA-occlusion, maximally on day 3. The change corresponds to the generation and resolution of brain edema monitored by MRI. The signals for the mRNA are predominantly observed in glial cells in the molecular and outer granular layer of the peri-infarcted cortex. These results indicate that AQP4 plays a role in post-ischemic edema formation.

Pre-exposure with low-dose UVA suppresses lesion development and enhances Th1 response in BALB/c mice infected with Leishmania (Leishmania) amazonensis.

This study was conducted to determine whether exposing mice to ultraviolet (UV) radiation would alter the pathogenesis of infection with Leishmania (Leishmania) amazonensis (L. amazonensis) which causes progressive cutaneous disease in susceptible mouse strains. BALB/c mice were irradiated with 10 and 30 J/cm(2) UVA on shaved skin of the back from Dermaray (M-DMR-100) for 4 consecutive days before infection with Leishmania promastigotes. The course of disease was recorded by measuring the size of lesions at various times after infection. Mice groups irradiated with UVA 10 and 30 J/cm(2) showed significantly suppressed lesion development compared with the non-irradiated mice. Light and electron microscopy revealed a few parasites at the site of inoculation in UVA-irradiated subjects. Sandwich enzyme-linked-immunosorbent-assay (ELISA) examination of sera showed dose dependently upregulated interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12, and downregulated interleukin (IL)-4 and interleukin (IL)-10 levels in UVA-irradiated as compared with the non-irradiated mice. Positive signals for IFN-gamma mRNA in irradiated mice were obtained by RT-PCR, while non-irradiated mice showed negative results. None of the examined samples showed signal for IL-4 mRNA. The present study disclosed that exposure of mice to different low-doses of UVA irradiation prior to infection may interfere with immunity to L. amazonensis in the murine model. This indicates that the cell-mediated response switch from Th2 to Th1 pattern suppressed the cutaneous lesions of L. amazonensis.

Distribution of endogenous tumour necrosis factor alpha in gliomas.

AIMS: To determine the distribution and cellular origin of endogenous tumour necrosis factor alpha (TNF alpha) in the cellular components of human gliomas. METHODS: Frozen sections of 26 gliomas (four astrocytomas (As); two oligoastrocytomas (OA); one ansplastic astrocytoma (AA); one anaplastic oligoastrocytoma (AOA); 18 glioblastomas (GB)) were examined immunohistochemically using antihuman TNF alpha and anti-Leu-M5 (CD11c) antibodies. Additional studies with double immunohistocchemical procedures were performed with anti-glial fibrillary acidic protein and anti-neurofilament antibodies. RESULTS: Eighty per cent of the AA, AOA, and GB (16 of 20) had a positive reaction for TNF alpha, but only 17% of As and OA (one of six) were positive. Positive cells were seen in both the tumour tissue and adjacent brain tissues. TNF alpha protein was detected not only in the tumour cells but also in the endothelium of tumour vessels as well as reactive astrocytes and neurons. CONCLUSIONS: Endogenous TNF alpha is present in cells of various origins in glial tumours including tumour vessels; however, the role of TNF alpha may be different in different types of cells or altered microenvironment.

Cellular expression of inducible nitric oxide synthase following rat cortical incision and its suppression by hydroxyl radical scavenger, 1,2-bis(nicotinamido)propane.

Cellular expression of an inducible isoform of nitric oxide synthase (iNOS) was studied immunohistochemically 1,3 and 7 days following rat cortical incision. The induction of iNOS was demonstrated almost exclusively in the macrophages accumulated within the incision cavity on day 3. They were significantly reduced in number by the treatment with 1,2-bis(nicotinamido)propane (P < 0.01), suggesting the involvement of hydroxyl radicals in the macrophage activation after cortical injury.

Reaction of microglial cells and macrophages after cortical incision in rats: effect of a synthesized free radical scavenger, (+/-)-N,N'-propylenedinicotinamide (AVS)

Reactive microglial cells and macrophages appear after trauma to the brain. To investigate the accumulation patterns of reactive microglial cells and macrophages after cortical incision, these cells were stained immunohistochemically with anti-ED1 antibody in the brain sections before and 1, 3, 5, and 7 days after incision. And to ascertain the participation of oxygen free radicals in these cellular reactions, a synthesized free radical scavenger, (+/-)-N,N'-propylenedinicotinamide (AVS) was administered in this model. Rats were administered AVS (300 mg/kg, i.p.) 30 min before, 2.5 h and every 24 h after incision (AVS group), while only saline was administered in the same manner as a control (saline group). In the saline group, both reactive microglial cells and macrophages had already appeared on day 1 post-incision. The former continued to increase in number during the following days, whereas the latter increased in number up to day 3 and thereafter decreased. Both the numbers of reactive microglial cells and macrophages were significantly decreased (P < 0.05) in the AVS group on days 5 and 7. The results suggest the participation of oxygen free radicals in the reaction of microglial cells and macrophages in traumatic brain injury.

Antiarrhythmic effects of an aconitine-like compound, TJN-505, on canine arrhythmia models.

We examined the effects of an aconitine-like compound, TJN-505 (1alpha-16beta-dimethoxy-20-ethyl-14alpha-(4-methox ybenzoyloxy)-aconitan-8,13-diol hydrochloride), on canine arrhythmias provoked by digitalis, two-stage coronary ligation, adrenaline, programmed electrical stimulation, or aconitine. TJN-505 (2-2.5 mg/kg i.v.) suppressed digitalis-, two-stage coronary ligation- and adrenaline-induced ventricular arrhythmias. The antiarrhythmic plasma concentrations (IC50) of TJN-505 for these arrhythmia models were 1.26, 0.94 and 1.31 microg/ml, respectively. TJN-505 (2 mg/kg i.v. followed by the infusion of 0.1 mg/kg per min) prolonged PR, QRS, QTc and JTc intervals and the ventricular effective refractory period and reduced the incidence of programmed electrical stimulation-induced arrhythmias in dogs with 7-day-old myocardial infarction (P < 0.05). TJN-505 (2 mg/kg i.v.) also suppressed the aconitine-induced atrial arrhythmias. In conclusion, TJN-505 suppressed various canine ventricular and atrial arrhythmias and seems to act as a blocker of multiple channels.

Progressive loss of messenger RNA and delayed neuronal death following transient cerebral ischemia in gerbils.

We examined mRNA, cytoplasmic RNA and structural damage in the hippocampus of the gerbil brain after transient ischemia by in situ hybridization, Acridine orange histochemistry and immunohistochemistry. Progressive decline of mRNA became visible in the CA1 region after reperfusion for 3 h and loss of cytoplasmic RNA and emergence of structural damage in 3 days. Reduction of mRNA in the CA3-CA4 region was transient. The findings suggested positive correlation between progressive loss of mRNA and delayed neuronal death.

Stochastic determination of the chromosomal region responsible for expression of human glial fibrillary acidic protein in astrocytic tumors.

Previous investigators have localized the human glial fibrillary acidic protein (GFAP) gene in the segment 17q21 in chromosome 17. In the present study, we statistically assessed the association between the allelic status in thirty-three microsatellite loci and the immunohistochemical expression of GFAP in twenty human astrocytic tumors. The results demonstrated that the loss of heterozygosity in only one locus (D17S795 located in 17q21.2) was significantly associated with the impaired expression of GFAP (P = 0.0280, Pc = 0.0384 by Fisher's exact test). The adjacent loci located in 17q21.1 and 17q21.3 were not relevant to GFAP expression. Those data suggest that the critical region responsible for GFAP expression (coding sequence and regulatory elements) is located close to the locus D17S795 in the segment 17q21.2.

Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat.

The effect of taste stimulation of Pinellia temata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve was observed in the anesthetized rat. Taste stimulation by Pinellia ternata (50 mg/ml, 10 min) resulted in a suppression in vagal gastric nerve activity. On the contrary, stimulation by Zingiberis rhizoma (50 mg/ml, 10 min) caused a facilitation in efferent activity. The mixture of Pinellia ternata and Zingiberis rhizoma (5:1, 50 mg/ml, 10 min stimulation) demonstrated no suppressive effect on gastric nerve activity. These observations indicate that it is reasonable to prescribe Pinellia ternata with Zingiberis rhizoma in traditional Japanese medicine to prevent suppressive effect of the taste of Pinellia ternata on gastric function.

Aberrant muscle activation in patients after resection of non-primary motor areas: demonstration by surface electromyography.

Two patients presented with a tumor involving mainly the supplementary motor area or the premotor cortex. Shortly after tumor resection, each developed transient impairment of voluntary movements. An electromyogram, with the skin electrodes placed over the muscles of the upper arms and forearms, demonstrated aberrant ipsilateral, contralateral or bilateral muscle activation during unilateral motor tasks in both patients. The bilateral activation was more prominent in the patient who had an intact dominant hemisphere. The present study suggests for the first time the importance of non-primary motor areas of the human brain in activating the proper set of muscles on the proper side of the body.

Saponins from the root of Bupleurum falcatum.

Three new saponins and nine known saponins were isolated from the dried roots of Bupleurum falcatum. On the basis of chemical and spectral analyses, the structures of new compounds, named 4''-O-acetylsaikosaponin d and hydroxysaikosaponins a and c, were established. In aqueous acidic conditions, saikosaponins a and d were converted into not only known compounds, saikosaponins b1 and b2, but also hydroxysaikosaponins a and d, respectively. Furthermore, quantitative analysis of the decoction of Bupleuri Radix itself by HPLC exhibited that it contained saikosaponins a, c and d, and hydroxysaikosaponins a, c and d.

Three acyclic bis-phenylpropane lignanamides from fruits of Cannabis sativa.

Three new acyclic bis-phenylpropane lignanamides, named cannabisin E, F and G were isolated from the fruits of Cannabis sativa. Their structures have been elucidated based on spectral and chemical evidence.

Effect of Pinellia ternata tuber on the efferent activity of the gastric vagus nerve in the rat.

Effect of intraduodenal infusion with the hot aqueous extract of Pinellia ternata tuber on the efferent discharges in the gastric branch of the vagus nerve was observed in the anesthetized rat. The infusion of the extract in doses of 2-15O mg per animal (c.a. 300 g, b.wt.) resulted in a dose-related increase in efferent activity of the vagal gastric nerve. The enhancement of the nerve activity following administration of 150 mg of this substance lasted longer than 90 min. It was observed that the suppressive effect on vagal gastric activity due to apomorphine and copper sulfate was antagonized by prior administration of the extract. From these observations it is suggested that Pinellia tuber acts as a facilitatory agent on gastric function.

Transforming growth factor-alpha, epidermal growth factor receptor, and proliferating potential in benign and malignant gliomas.

Surgical specimens from six benign and 16 malignant human gliomas were investigated immunohistochemically to correlate the degree of malignancy, the distribution of transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor, and the potential for cell proliferation using monoclonal antibodies to TGF-alpha, EGF receptor, and Ki-67. Fourteen (88%) of the malignant gliomas and one (17%) of the benign gliomas were found to be positive for TGF-alpha, and 14 (88%) of the malignant gliomas and two (33%) of the benign gliomas expressed EGF receptor. The proliferation index with Ki-67 was 18.8% +/- 8.1% (mean +/- standard deviation) in malignant gliomas and 1.9% +/- 1.8% in benign gliomas. In general, cells positive for EGF receptor and Ki-67 were randomly distributed throughout the tumor tissue, and cells positive for TGF-alpha tended to be clustered without obvious relationship to areas of necrosis or blood vessels. In some tumors, cells positive for TGF-alpha, EGF receptor, and Ki-67 were associated in a focal distribution. The more frequent expression of TGF-alpha and EGF receptor in the highly proliferative malignant gliomas is compatible with a role for TGF-alpha and EGF receptor in the induction or stimulation of malignant gliomas.

A giant intracranial mucocele associated with an orbitoethmoidal osteoma. Case report.

The authors present a rare case of a giant intracranial mucocele associated with an orbitoethmoidal osteoma in a patient suffering from a generalized convulsive disorder. The broad pedicle of the osteoma had penetrated the cribriform plate and extended intracranially to form a nodular mass in the olfactory groove. The intracranial portion of the osteoma was surrounded by a mucocele. Both the cyst wall and multilayered intracystic septations of the mucocele were indented by layers of the osteoma. Although the extracranial portion adhered to the mucosa of the ethmoidal sinus, there were no signs of sinus obstruction. No direct communication other than the osteoma was identified between the mucocele and the ethmoidal mucosa. The large cerebral defect, which the mucocele occupied, communicated directly with the lateral ventricle without any intervening membranous structures. A frontal craniotomy is recommended for exposure of the lesion and plastic repair of the dural defect.