Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The research thus far on the relation of the immune system to gliomas has shown that a glioma associated antigen does exist. Small quantities of glioma associated antibodies probably circulate within the patient's serum but there is definite evidence of depression of the cell-mediated vanguard of the immune response. This depression is caused by a blocking factor that may be present as an antigen, antibody, or antigen-antibody complex. Both active and passive immunotherapeutic techniques have been employed in a small number of patients with little success. Considerable understanding of the alteration of the immune system is necessary before a rational approach toward immunotherapy of gliomas may be undertaken. However, it is apparent that reductive therapy consisting of surgery, radiation, and chemotherapy will be necessary before the immune system will be effective against the tumor burden.
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PMID:Tumor immunology: a neurosurgical perspective. II. The immunology of glial neoplasms. 7 64

The antitumor agent chloroethylcyclohexyl-nitrosourea (CCNU) was examined using a rat glioma model. A i.p. administration of three times 40 mg/kg CCNU was highly effective and increased the life-span of tumor-bearing rats from 53 to 86%. A total quantity of CCNU amounting to less than 30 mg/kg was not effective. On the other hand, large dosages exceeding LD10 proved to be toxic. The depression of platelets and white blood cells was mild after a single dosage of 40 mg/kg CCNU which recovered on about the 6th day. In the CCNU-treated animals there was an increase of the extent of necrobiosis. Ballooning of tumor cells with nuclear pyknoses and a lack of mitotic features occurred. Microcystic changes appeared sometimes to be more frequent than in control groups.
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PMID:Brain tumor chemotherapy using a rat glioma model. 46 98

1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino-1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. 140 9

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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PMID:Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. 179 58

Brainstem acoustic evoked potentials (BAEPs) were measured in 14 children with different type of posterior fossa tumours several times during the clinical course, in order to assess the value of this simple and non-invasive method in the diagnosis and follow-up of posterior fossa tumours in childhood. Eight children had midline medulloblastoma, three children had lateral astrocytoma, three had intrinsic brainstem glioma. Different BAEP patterns could be detected in different tumour's type: bilateral symmetrical or slightly asymmetrical I-V. IPL prolongation in midline medulloblastomas, unilateral or markedly asymmetrical I.-V. IPL prolongation or wave V. depression on the contralateral side in lateral astrocytomas, and severely distorted asymmetrical waveform in intrinsic brainstem gliomas. The BAEPs were abnormal earlier than CT scan in a case of craniospinal astrocytoma. BAEPs were useful in the follow-up: the effect of the preoperative chemotherapy or the progression of the inoperable tumours could be as well documented by this method, as by the CT scan. BAEPs proved effective in the assessment of postoperative neurological complications: bilateral symmetrical IPL prolongation and wave V. depression with clinical signs of increased intracranial pressure occurred in a case of postoperative occlusive hydrocephalus, unilateral IPL prolongation occurred during irradiation or chemotherapy after medulloblastoma removal as signs of cerebral oedema.
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PMID:Value of brainstem acoustic evoked potentials in posterior fossa tumours in childhood. 186 81

Many studies have suggested the possible existence of tumor-associated antigens in brain gliomas. Strong evidence for the existence of such cell determinants was provided by recent investigations using hybridoma technology. The possibility of obtaining monoclonal antibodies (MAbs) against glioma-associated antigens should help to allow their identification, purification, and characterization. Utilizing MAbs as reagents of predefined specificity, a number of central and peripheral nervous system antigens could be detected. The molecules recognized by MAbs in glioma cells can be subdivided into four categories: [1] biochemical defined proteins, [2] specificities shared by nervous system-lymphoid cells, [3] oncoembryonic-oncofetal determinants, and [4] tumor-restricted antigens. Of greater significance is the heterogeneity of antigen expression among various individual glioma cells observed in frozen sections of tumor biopsies. Using a panel of MAbs, the phenotypic heterogeneity, i.e., the variation in antigen expression can be documented within and among malignant gliomas and cell lines derived from them. In spite of this the characteristic pattern of antibody binding to brain tumors makes MAbs the potentially best reagents for immuno-histochemical application in surgical neuropathology. Moreover, immuno-cytological screening of tumor cells in the cerebrospinal fluid has also proved to be valuable. The localization of radio-labelled MAbs in experimental and human gliomas growing subcutaneously and intracranially in athymic nude mice were explored by radioscintigraphy and autoradiography. Imaging experiments with 131I-labelled MAbs recognizing epitopes on the glioma cell surface showed high levels of specific activity in xenografts. Preliminary data indicate that administration of 131I-MAbs as well as drug conjugates (daunomycin-MAbs) causes a depression of glioma cell proliferation in vitro as well as delayed tumor growth and thus prolonged survival time of tumor-bearing mice. The mechanisms of antibody delivery and transport of "immunotoxins" from the vascular compartment to intracerebral tumor tissue are presently a subject of discussion. The complexity of this area necessitates comprehensive experimental work in order to define the factors involved in the delivery of MAbs to brain to tumor tissue and thus optimize the rate of blood-to-tumor transport. Current investigations have shown that it is possible to image malignant human gliomas using radio-labelled antibodies. The next step will be to attain target immunotherapy. The use of MAbs as carrier molecules for clinical applications might soon be possible.
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PMID:Monoclonal antibodies in neuro-oncology. 218 45

Brainstem acoustic evoked potentials (BAEPs) were recorded in 16 children with posterior fossa tumours. The results were compared with the clinical course, CT scan findings and the postmortem pathological findings. Eight children had midline medulloblastoma, four children had lateral astrocytoma (two of them cerebellar, one of them pontocerebellar, and one of them craniospinal) and four children had brainstem glioma. Different BAEP pattern could be detected according to the tumour's location and histological nature: 1. In midline medulloblastoma: bilateral, symmetrical, or slightly asymmetrical I-V. IPL prolongation was the common abnormality. Beside that, some of the patients showed III-V., or I-III. IPL prolongation, or V. depression. 2. In lateral astrocytoma: asymmetrical BAEP abnormalities were seen: unilateral V. depression, and/or I-V. IPL prolongation. 3. In brainstem glioma: severely distorted waveform could be observed, with depression and gradual disappearance of components following the wave III. Based on these results BAEP measurement seems to be useful in the differential diagnosis of posterior fossa tumours of childhood, and it can be necessary even beside the CT scan. It can be useful in the early diagnosis, because the BAEP positivity can precede the CT scan positivity, in such a case repeated CT scan required. Finally BAEP measurement proved to be effective in the follow-up of posterior fossa tumours: it can document the tumour's chemotherapeutic regression, or the progression. It is a simple, non-invasive, and cheap method.
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PMID:[Brainstem acoustic evoked potential (BEAP] in children with posterior fossa tumors]. 231 75

The action of phenytoin on the inward calcium current (ICa) was studied in cells of the clonal mouse neuroblastoma X rat glioma hybrid line 108CC5 by the suction pipette technique for internal perfusion and voltage clamp. The ICa was recorded after suppression of Na+ and K+ currents. Phenytoin, applied externally in concentrations of 50 to 500 microM, depressed the ICa in the investigated potential range of -60 to +30 mV in a concentration-dependent manner. When the cells were stimulated by depolarizing clamp steps, the extent of the ICa depression increased with the frequency and duration of the activating pulses. ICa was also inhibited on intracellular application of phenytoin.
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PMID:Calcium channel block by phenytoin in neuroblastoma x glioma hybrid cells. 241 95

Mechanism of methylmercury cytotoxicity was investigated with special reference to its preferential action on microtubules and protein biosynthesis in cultured cells. The tubulin synthesis analyzed by autoradiography of two-dimensional electropherogram using 35S-methionine was inhibited by 50-70% in mouse glioma cells exposed to 5 x 10(-6) M methylmercury for 3 h, which almost completely depolymerized microtubules. Total protein synthesis monitored by incorporation of labeled methionine into acid insoluble fraction was decreased slightly but significantly and the protein bands other than tubulin on gradient urea-PAGE gel appeared to remain unchanged under the experimental condition used. These results suggest that the inhibition of protein synthesis observed on exposure to methylmercury can be ascribed, at least partly, to a possible autoregulatory depression in tubulin synthesis owing to the increase in the pool of tubulin subunits resulted from microtubule depolymerization by methylmercury.
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PMID:Mechanism of cytotoxicity of methylmercury. With special reference to microtubule disruption. 248 6

It is known that nerve growth factor (NGF) induces neurite outgrowth and elevation of the activity of adrenergic marker enzyme, tyrosine hydroxylase (TH) in clonal rat pheochromocytoma cells (PC12), whereas glioma-conditioned medium (GCM) induces neurite outgrowth and elevation of the activity of cholinergic marker enzyme, choline acetyltransferase (ChAT) in PC12 cells. In the previous study we have shown that retinoic acid (RA) induces specific elevation of ChAT activity and depression of TH activity without morphological differentiation (Matsuoka, I. et al., Brain Res., 502 (1989]. In the present study, we compared the effects of NGF, GCM and RA on the intracellular signalings in PC12 cells in relation to the mechanism of cholinergic differentiation. Addition of NGF, GCM or RA to the culture medium of PC12 cells caused a rapid rise in intracellular Ca2+ concentration [( Ca2+]i) reaching the level of almost 2.5-fold the resting condition within 3-18 h. Thereafter, [Ca2+]i of NGF-treated cells were decreased to the resting level within 12 h. On the other hand, [Ca2+]i of GCM-and RA-treated cells decreased to a level which was 1.8- to 2-fold the resting condition within 24-48 h and stayed at this level for up to 4-7 days. When homogenates of GCM- and RA-treated PC12 cells were incubated with [gamma-32P]ATP, phosphorylation of a protein with molecular mass of 27 kDa (27 K-protein) was specifically enhanced. The phosphorylation of the 27 K-protein was not seen in the homogenate of the NGF-treated cells. The phosphorylation of the 27 K-protein was dependent on Ca2+ and inhibited by inhibitors of Ca2+-dependent protein kinase, H-7 and W-7. Addition of H-7 and W-7 to the culture medium of PC12 cells abolished the elevation of ChAT activity specifically induced by GCM and RA. These observations suggested that the sustained increase of [Ca2+]i and Ca2+-dependent protein phosphorylation are involved in the intracellular signaling mechanism required for the cholinergic differentiation of PC12 cells induced by GCM and RA.
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PMID:Possible involvements of intracellular Ca2+ and Ca2+ -dependent protein phosphorylation in cholinergic differentiation of clonal rat pheochromocytoma cells (PC12) induced by glioma-conditioned medium and retinoic acid. 258


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