Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cefotiam (CTM) was evaluated for its safety and efficacy in children. Twenty-six patients were treated with 40 to 200 mg/kg per day of CTM by intravenous administrations. The diagnosis of the patients were acute pharyngitis (2), acute bronchitis (1), pneumonia (4), empyema (2), urinary tract infection (2), typhoid fever (1), acute enterocolitis (2), partially-treated purulent meningitis (1), and suspected septicemia in neuroblastoma (1); and the remaining ten patients were considered to have nonbacterial infections. The pathogens recovered were Streptococcus pyogenes (1), Streptococcus pneumoniae (1), Staphylococcus aureus (4), Haemophilus influenzae (4), Escherichia coli (1), enteropathogenic Escherichia coli (1), Salmonella typhi (1), and Campylobacter jejuni (1). All but two patients of bacterial infections were cured after the CTM therapy, and the rate of efficacy was 87.5%. Diarrhea (3), urticaria (1), transient elevation of GOT and GPT (1), and transient eosinophilia (3) were found to be associated with the CTM therapy. However, no severe adverse reactions were encountered. Half life of the serum CTM level was 0.93 +/- 0.13 hours, and excretion into the urine was rapid. CSF concentration obtained 1 hour after an intravenous injection of 21 mg/kg of CTM in a case with inflamed meninges was 1.5 mcg/ml, and the CSF/serum ratio was 9.0%. From these data, CTM appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections.
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PMID:[Clinical evaluation of cefotiam therapy in children (author's transl)]. 627 Apr 13

The metabolism of L-tryptophan to the neuroactive kynurenine pathway metabolites, L-kynurenine, kynurenate and quinolinate, and the effects of two inhibitors of quinolinate synthesis (6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate) were investigated by mass spectrometric assays in cultured cells and in vivo. Cell lines obtained from astrocytoma, neuroblastoma, macrophage/monocytes, lung, and liver metabolized L-[13C6]-tryptophan to L-[13C6]kynurenine and [13C6]kynurenate, particularly after indoleamine-2,3-dioxygenase induction by interferon-gamma. Kynurenine aminotransferase activity was measurable in all cell types examined but was unaffected by interferon-gamma. These results suggest that many cell types can be sources of kynurenate following immune activation. In vivo synthesis of L-[13C6]kynurenine and [13C6]kynurenate from L-[13C6]tryptophan was studied in the CSF of macaques infected with poliovirus, as a model of inflammatory neurologic disease. The effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate on the synthesis of kynurenate were different. 6-Chlorotryptophan attenuated formation of L-[13C6]kynurenine and [13C6]kynurenate and was converted to 4-chlorokynurenine and 7-chlorokynurenate. It may be an effective prodrug for the delivery of 7-chlorokynurenate, which is a potent antagonist of NMDA receptors. In contrast, 4-chloro-3-hydroxyanthranilate did not reduce accumulation of L-[13C6]kynurenine and [13C6]kynurenate. 6-Chlorotryptophan and 4-chloro-3-hydroxyanthranilate are useful tools to manipulate concentrations of quinolinate and kynurenate in the animal models of neurologic disease to evaluate physiological roles of these neuroactive metabolites.
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PMID:Metabolism of L-tryptophan to kynurenate and quinolinate in the central nervous system: effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. 759 10

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.
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PMID:High dose cyclophosphamide: stem cell mobilizing capacity in 21 patients. 792 Feb 30

The approximately 4 kD (39-43 amino acid) polypeptide (amyloid beta protein, A beta) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursor proteins collectively referred to as the amyloid beta-protein precursor (beta APP). Using immunoblotting techniques, metabolic labeling, and sequencing we have analyzed beta APP derivatives in medium conditioned by: (1) human mononuclear leukemic (K562) cells expressing a model beta AP-bearing carboxyl-terminal beta APP derivative (2) human neuroblastoma (M17) cells transfected with constructs expressing full length beta APP and (3) M17 cells expressing only endogenous beta APP. In each case, we observed the release of a approximately 4 kD beta APP derivative essentially identical to the A beta found in AD amyloid. A similar, if not identical, beta APP fragment was readily detected in CSF from both Alzheimer's disease patients and controls. These observations indicate that the A beta is produced and released by normal processing of the beta APP. To determine if the production of A beta or A beta-tearing COOH-terminal beta APP derivatives is altered in cells expressing the mutant beta APPs linked to familial AD, we have compared M17 cells expressing wild type beta APP with those expressing mutant beta APPs (beta APP delta I or beta APP delta NL). After continuous metabolic labeling for 8 hours, cells expressing the beta APP delta NL mutant showed a 5-fold increase in the relative amount of an approximately 11.4 kD A beta-bearing carboxyl-terminal beta APP derivative, and they released 6-fold more 4 kD A beta into the medium. These observations provide strong evidence that: (1) the pathway producing A beta in cultured cells is highly relevant to AD and (2) the beta APP delta NL mutant causes AD because its processing is altered in a way that releases increased amounts of A beta.
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PMID:Production of amyloid beta protein from normal amyloid beta-protein precursor (beta APP) and the mutated beta APPS linked to familial Alzheimer's disease. 823 66

We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize antigens of the patient's own tumor.
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PMID:Antineuronal antibody in a patient with neuroblastoma and opsoclonus-myoclonus-ataxia: a case report. 926 93

Autopsy studies of patients with AIDS dementia have shown neuronal loss consistent with a neurotoxic component of this disease. In vitro studies suggest that viral products or cytokines from HIV-infected macrophages (Mphi) may modulate or directly mediate excitotoxic cell death of neurons. Mphi differentiated from peripheral mononuclear blood cultures were infected with HIV, and conditioned media (CM) were harvested from these cultures. Exposure of SK-N-MC (neuroblastoma) cells to CM from HIV-infected Mphi for 4, 24 or > or = 48 h resulted in a mean suppression of 12-34% of the glutamate transport Vmax with no appreciable change in transport Km. An astrocytoma tumor cell, U373MG, showed similar CM-mediated glutamate uptake suppression. Changes were evident in total and Na+-dependent glutamate uptake, with significantly more suppression of Na+-dependent uptake. Similar effects were seen with the nonmetabolizable transporter agonist D-aspartate, indicating that the effect was on transport and not metabolism. No suppression was seen with CM from uninfected Mphi or Mphi infected with heat-inactivated HIV. The magnitude of uptake suppression was not correlated with CM p24 values, and removal of CM virions by ultracentrifugation and immunoprecipitation did not alter the uptake-suppressive properties of infected Mphi CM. Uptake suppression was seen when Mphi were infected with Mphi-tropic strains HIV(SF162), HIV(JR-CSF), HIV(NFN-SX) and a Mphi-tropic patient isolate, but not the lymphotropic strain HIV(LAI). HIV-infected Mphi may produce substances which suppress neuronal and glial glutamate neurotransmitter uptake, resulting in higher extracellular glutamate levels and leading possibly to deficits in cell signaling and neurotoxicity.
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PMID:HIV decreases glutamate transport in SK-N-MC neuroblastoma cells. 953 Oct 13

We have examined vaccination effects of cytokine-producing murine neuroblastoma cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established. Their in vitro proliferation rates and the class I expression of major histocompatibility complex were not different from those of wild-type cells. Five-Gy irradiation of the respective cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In contrast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngeneic mice with irradiated wild-type cells as a control or cytokine-producing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, on the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF-expressing syngeneic tumor cells can be potentially used as a tumor vaccine by inducing protective immunity against low immunogenic neuroblastomas in the inoculated hosts.
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PMID:Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor. 962 5

Alzheimer disease (AD) has polyetiology. Independent of the etiology the disease is characterized histopathologically by the intraneuronal accumulation of paired helical filaments (PHF), forming neurofibrillary tangles, neuropil threads and dystrophic neurites surrounding the extracellular deposits of beta-amyloid in plaques, the second major lesion. The clincal expression of AD correlates with the presence of neurofibrillary degeneration; beta-amyloid alone does not produce the disease clinically. Thus arresting neurofibrillary degeneration offers a promising key target for therapeutic intervention of AD. The major protein subunit of PHF is the microtubule-associated protein tau. Tau in AD brain, especially PHF, is abnormally hyperphosphorylated and glycosylated. With maturation, the tangles are increasingly ubiquitinated. Levels of tau and conjugated ubiquitin are elevated both in AD brain and CSF. The AD abnormally phosphorylated tau (AD P-tau) does not promote microtubule assembly, but on dephosphorylation its microtubule promoting activity is restored to approximately that of the normal tau. The AD P-tau competes with tubulin in binding to normal tau, MAP1 and MAP2 and inhibits their microtubule assembly promoting activities. Furthermore, the AD P-tau sequesters normal MAPs from microtubules. The association of AD P-tau with normal tau but not with MAP1 or MAP2 results in the formation of tangles of 3.3 +/- 0.5 mm filaments. Deglycosylation of Alzheimer neurofibrillary tangles with endoglycosidase F/N-glycosidase F untwists the PHF resulting in tangles of thin filaments similar to those formed by association between the AD P-tau and normal tau. Dephosphorylation or deglycosylation plus dephosphorylation but not deglycosylation alone restores the microtubule assembly promoting activity of tau. In vitro AD P-tau can be dephosphorylated by protein phosphatases PP-2B, PP-2A and PP-1 but not PP-2C and all the three tau phosphatases are present in brain neurons. Tau phosphatase activity is decreased by approximately 30% in AD brain. Inhibition of PP-2A and PP-1 activities in SY5Y neuroblastoma by 10 nM okadaic acid causes breakdown of microtubules and the degeneration of these cells. It is suggested (I) that a defect(s) in the protein phosphorylation/dephosphorylation system(s) leads to a hyperphosphorylation of tau, (ii) that this altered tau causes disassembly of microtubules and consequently a retrograde neuronal degeneration; (iii) a pharmacological approach to AD is to enhance the tau phosphatase activity; and (iv) that CSF tau and conjugated ubiquitin levels are promising markers of AD brain pathology.
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PMID:Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles. 970 Jun 55

Cerebrospinal fluid from L-dopa-treated Parkinson's disease patients and subjects without neurodegenerative diseases (controls) was explored in its trophic properties as culture medium on a variety of cells from neural origin. Primary cultures of regional brain dissociates from rat and Cebus apella monkey fetuses, immature rat adrenal chromaffin cells, phaeochromocytoma (PC12), and neuroblastoma (NB69) cell lines as well as subcultured fetal rat astroglia were used as target cells for 24- to 48-h culture periods. Most cerebrospinal fluid samples from L-dopa-treated patients had a general dystrophic effect. This phenomenon was more apparent on striatum and ventral mesencephalon than on cerebral cortex cell dissociates. The deleterious effect of these samples was abolished by previous exposure to fetal astroglial cells. Neuroblastoma cells showed no differential response when exposed to samples from control and L-dopa-treated patients. Phaeochromocytoma cells did not grow processes under any of the samples assayed in the time interval explored, but neither showed evidence of dystrophy. The relevance of these findings to the transplantation of different cell types as one of the possible therapies for Parkinson's disease is discussed. The suggestion is made that CSF testing prior to transplantation may aid in anticipating its possible outcome. Cotransplantation of neuronal cells with subcultured astroglia may foster survival and growth of the former cells.
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PMID:Cerebrospinal fluid from L-dopa-treated Parkinson's disease patients is dystrophic for various neural cell types ex vivo: effects of astroglia. 987 81

The purpose of this study was to determine the feasibility and assess optimal timing of harvesting peripheral blood stem cells (PBSC) for transplantation in young children. Thirteen children with body weight less than 25 kg, mean age of 3.9 years (1-9 yrs) who had recurrent solid tumors and leukemia were given tumor specific chemotherapy followed by i.v. rhG-CSF (5 microg/kg/d) for stem cell mobilization. Cytaphereses were done through a central venous line (CVL) during the marrow recovery phase (WBC >0.5 x 10(9)/l). The phereses were analyzed separately and assigned to three groups depending on the WBC at the time of the pheresis: Group I (WBC <1.0 x 10(9)/l), Group II [WBC in the range 1.0-3.0 x 10(9)/l] and Group III (WBC >3.0 x 10(9)/l). Samples from each harvest were assayed for cell count, CFU-GM, BFU-E, CD34+ cell count, and tumor cell immunocytology in patients with neuroblastoma (NBL). A median of 3.2 x 10(8) mononuclear cells per kg (MNC/kg), [mean 2.8 x 10(8) MNC/kg, standard error of the mean (SEM) +/- 0.74 (1.1-4.7)] were infused following myeloablative therapy. 78 phereses were performed in 13 children with a median weight of 18 kg (10-25 kg). A median of 5 phereses were performed per patient. There were no significant differences in the percentage and number of CD34+ cells, CFU-GM or BFU-E colonies assayed by plating 0.5 x 10(5) cells. Differences could be found in the total number of MNC (p<0.008) and the number of MNC/kg (p<0.001) between Groups II and III. No tumor cell contamination was detected in the NBL patients by immunocytology. All patients were rescued with PBSC and achieved sustained white cell engraftment (ANC >0.5 x 10(9)/l) at a median of 13.5 d (10-25 d) and platelet engraftment (untransfused platelet count >20.0 x 10(9)/l) at a median of 29 d (12-63 d). The only toxicity encountered during the phereses was thrombocytopenia in 4 patients whose median post-pheresis platelet count was 6.0 x 10(9)/l (3.0-9.01). It is concluded that collection of PBSC in young children is feasible and safe and can be performed through a cuffed CVL at the time of WBC recovery post mobilization with chemotherapy and G-CSF. Cytopheresis can be effectively performed when the peripheral WBC count approaches 1.0 x 10(9)/l. Following stem cell infusion, engraftment was prompt and durable.
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PMID:Peripheral blood stem cell transplantation in young children: experience with harvesting, mobilization and engraftment. 1008 41


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