Finding gluon jets with a neural trigger.
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Journal Article↗
Biomedical subjects
C Peterson
Publications and source records attributed to C Peterson.
Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro.
1,2,3,4-Tetrahydro-5-aminoacridine (THA; tacrine) reportedly improves cognitive deficits in certain individuals with Alzheimer's disease. The present study describes increased glucose oxidation and acetylcholine (ACh) synthesis by mouse brain slices after THA treatment. THA increased [U-14C]glucose decarboxylation and ACh formation in a concentration-dependent manner in hippocampal slices (50 nM less than 50 microM less than microM). In striatal and cortical slices, 50 microM THA effectively elevated the oxidation of glucose and its incorporation into ACh. Thus the efficacy of THA treatment on Alzheimer patients may be partially related to increased ACh synthesis and oxidative metabolism.
Acetylcholine↗
Comparison of high-dose therapy and autologous bone marrow transplantation for T-cell and B-cell non-Hodgkin's lymphomas.
Advanced T-cell non-Hodgkin's lymphoma in adults has been found to have a poor outlook with conventional chemotherapy. To see if this extends to patients treated with high dose therapy and autologous hematopoietic stem cell transplantation, we reviewed the results with this treatment approach at our institution. From October, 1983, to May, 1988, 41 patients who underwent high-dose therapy and autologous hematopoietic stem cell transplant for recurrent non-Hodgkin's lymphoma were re-biopsied before transplantation to determine their immunophenotype. Seventeen of these patients were found to have a T-cell lymphoma, and 24 had a B-cell lymphoma. All patients were included in the intermediate or high grade non-Hodgkin's lymphoma categories, and none were histologically transformed from a low grade lymphoma. Analysis of the response to autologous transplantation in these two patient populations revealed a slightly better complete response rate for patients with T-cell lymphoma (ie, 59% versus 42%, P = NS). The actuarial 2-year survival was 35% in the T-cell group compared with 30% in the B-cell group (P = NS). The 2-year disease-free survival was 28% for the T-cell and 17% for the B-cell patients. Our results with autologous transplantation for salvage therapy revealed equivalent long-term survival and disease-free survival in both relapsed T- and B-cell non-Hodgkin's lymphoma.
Adolescent↗
Decreased survival of hippocampal neurons in medium conditioned by fibroblasts from aged and Alzheimer donors.
Medium conditioned by fibroblasts promotes survival and neurite outgrowth of cultured hippocampal neurons. Sub-confluent cultures of cells from normal young, aged and Alzheimer donors conditioned serum-free medium for 2 days. Hippocampal neurons from 18- to 19-day-old embryos were maintained in medium conditioned by skin fibroblasts from young, aged or Alzheimer donors. One, 4 and 7 days after plating the cells were examined for morphological differences. Neuron survival four days after plating was found to be the highest in medium conditioned by young greater than aged greater than Alzheimer cells. These findings suggest that both aged and Alzheimer donors secrete less of the substances that are necessary for survival and neurite outgrowth of hippocampal neurons. This provides further evidence that non-neuronal cells demonstrate abnormalities during aging and Alzheimer's disease.
Aging↗
Increased spectrin proteolysis in the brindled mouse brain.
Proteolytically generated fragments of the microfilament anchoring protein brain spectrin were found to accumulate in brindled mouse brain. Proteolysis was most extensive in brain regions possessing high concentrations of N-methyl-D-aspartate (NMDA) receptors (e.g. cortex, striatum, hippocampus). The brindle mutation affects copper homeostasis and thus a variety of copper-dependent enzymes needed in intermediary metabolism. The altered mitochondria of these mice are suggested to less efficiently buffer NMDA receptor-gated calcium fluxes, thus promoting activation of calcium-activated proteases and subsequent degradation of the spectrin meshwork.
Aging↗
On the paradoxically concentration-dependent metabolism of 6-mercaptopurine in WEHI-3b murine leukemia cells.
The intracellular metabolism of 6-mercaptopurine (6-MP) was studied in a murine leukemia cell line, WEHI-3b. Cells were incubated 3 to 24 h with 10 nM to 50 microM 6-MP. Nucleotides were extracted with perchloric acid, and the 6-thiopurine nucleotides were isolated on mercurial cellulose. The endogenous ribonucleotides in the perchloric acid extracts as well as 6-thiopurine nucleotides were separated and quantified with anion exchange high-performance liquid chromatography. The concentration of 6-thioinosinate (6-TIMP) and 6-thioxantinate (6-TXMP) increased with an increasing 6-MP dose. The concentration of the 6-thioguanosine nucleotides (6-TGN) increased with 6-MP concentrations between 10 nM and 1 microM. However, further increase in 6-MP concentration led to a decrease in the formation of 6-TGN. At 50 microM 6-MP, the concentration of 6-thioguanosine 5'-triphosphate was one fifth of that seen at 1 microM. The incorporation of 6-[35S]mercaptopurine into DNA was also slightly higher at 1 microM compared with 50 microM. The cytocidal effect on clonogenic cells was one log greater at 1 microM 6-MP compared with 50 microM 6-MP. The decrease of 6-TGN was accompanied not only by an increased 6-TIMP concentration but also by an inhibition of the purine de novo synthesis and consequently by a decrease of the cellular ATP concentration. The ATP concentration in the cells treated with 1 microM 6-MP could be reduced to the level seen in cells treated with 50 microM 6-MP by simultaneous incubation with 0.3 microM antimycin A. This decrease of ATP concentration was accompanied by a reduction of 6-TGN and to a lesser extent of 6-TXMP. These experiments suggest that the "self-limiting" phenomenon in the metabolism of 6-MP might be caused by a depletion of ATP by inhibition of purine de novo synthesis presumably by 6-TIMP.
Animals↗
Pharmacokinetics of cytosine arabinoside in cerebrospinal fluid and of its metabolite in leukemic cells.
Concentrations of ara-CTP in leukemic cells isolated from CSF and of ara-C in lumbar CSF were measured following intraventricular ara-C administration in two girls with refractory meningeal leukemia. CSF samples were collected with a permanent intrathecal-lumbar catheter. In contrast to the comparatively short retention of ara-C in the CSF (t1/2 1.8 to 2.9 hours), there was a high accumulation and an extremely long retention of ara-CTP in the leukemic cells (t1/2 8.1 to 36 hours). The patients included in this study had an ara-C-resistant disease. No obvious relationship was seen between concentrations of ara-C in the CSF and of ara-CTP in the leukemic cells. Similar studies were performed after simultaneous intraventricular administration of hydrocortison and ara-C. Hydrocortison did not increase ara-CTP retention in the leukemic cells, nor did it effect CSF pleocytosis.
Arabinofuranosylcytosine Triphosphate↗
Uptake of adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas.
Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0.9 and 4.6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient. In an in vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.
Adult↗
A comparative study of autistic subjects' performance at two levels of visual and cognitive perspective taking.
This study extended previous investigations of autistic subjects' perspective-taking abilities through a within-subjects contrast between two levels each of both visual and cognitive problems with stringent controls against guessing. When compared with normal and mentally retarded subjects', the autistic group's performance supported Baron-Cohen's (1988) hypothesis of a selective deficit for cognitive perspective taking among autistic subjects. Both levels of visual perspective taking demonstrated virtually unimpaired performance for autistic subjects with no significant difference between them and control groups. On the cognitive perspective-taking tasks, however, the performance of the three groups was significantly different, with the vast majority of autistic subjects unable to do even the most basic level of this task. Possible explanations and educational implications were discussed.
Adolescent↗
Pessimistic explanatory style and response to illness.
Previous studies have shown that a pessimistic explanatory style is a risk factor for illness, but the factors linking explanatory style and illness are unknown. One's characteristic response to poor health may mediate this relationship. Perhaps pessimistic individuals act helplessly in the face of their symptoms, thereby exacerbating disease. In the present study, we investigated this possibility by asking 96 young adults to complete measures of explanatory style, habitual response to illness, and ways of coping during their most recent episode of illness. Subjects who explain bad events pessimistically (with internal, stable, and global causes) reported more frequent illnesses during the past year and rated their overall health more poorly than those who habitually favor external, unstable, and specific explanations. When ill, the pessimistic subjects were less likely than their optimistic counterparts to take active steps to combat their illness. Our results suggest that one pathway leading from pessimistic explanatory style to poor health is mundane: passivity in the face of disease.
Adult↗
Explanatory style and gambling: how pessimists respond to losing wagers.
Fifty-three patrons of a harness racing track completed two measures of explanatory style prior to an afternoon's races. One measure assessed general explanatory style, using bad events taken from the Attributional Style Questionnaire, and the other measure assessed betting-specific explanatory style, using bad events specific to harness race betting. Subjects then kept a diary during the first eight races. After each race, they reported how much they had bet, whether they had won or lost, the major cause of the outcome, their confidence about winning future bets, and whether they were ruminating about past or future races. Explanatory style assessed in both ways had similar correlates. Explanatory style predicted the specific attributions made by subjects for losses. Pessimistic explanatory style (internal + stable + global attributions) predicted rumination following a lost bet, but it was unrelated to expressed confidence. Rumination after a loss was in turn associated with larger wagers on subsequent races and a tendency toward less successful wagers. These results clarify one way in which pessimistic explanatory style results in helplessness, and suggest a path by which problematic gambling may develop.
Adaptation, Psychological↗
The who, when and where of early narratives.
To be well understood, narratives need to be embedded within appropriate contextual information. The early development of key orientation (participants, location and time) was traced with an 18-month longitudinal study of real-experience narratives produced by 10 children aged approximately 2-3;6. Listener knowledge or inference was required to decode most named participants and many were not specified at all. There was no developmental improvement. Orientation to WHEN was rare at first and involved formula words indiscriminately applied. There was steady developmental improvement in frequency as well as differentiation of time references. WHERE information was more common at all ages, particularly when the narrated events occurred away from home. It also showed developmental improvement, but only for away-from-home locations. Overall, very young children can produce narratives in an unscaffolded context to adults unfamiliar with their experiences. The potential role of parental scaffolding in teaching orientation skills is discussed.
Child Language↗
Bulimia and taste: possible interactions.
Potential abnormalities of taste were examined in bulimic subjects who purged by vomiting and in controls. When spatial testing of the tongue and palate was performed by direct local application of sweet, salty, sour, and bitter solutions, bulimics showed a selective spatial loss on the palate. The palate may be affected by purging because vomit is directed toward the roof of the mouth where the palate receptors are located. The data suggest that the acid in vomit damages these receptors. Bulimics and controls did not differ in their basal ratings of intensity or pleasantness of sweet, salty, sour, and bitter stimuli when these were sipped rather than directly applied to the tongue. However, after ingesting a glucose load, controls found sweet taste significantly less pleasant, whereas bulimics did not. The results suggest that bulimics may also have an abnormal experience of satiety.
Adolescent↗
Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex.
Previous studies have shown that human leukaemic cells and certain tumour tissues have a higher receptor-mediated uptake of low density lipoprotein (LDL) than the corresponding normal cells or tissues. LDL has therefore been proposed as a carrier for anti-cancer agents. In the current study, a water-insoluble mitoclomine derivative (WB 4291) was incorporated into LDL. The WB 4291-LDL complex contained about 1,500 drug molecules per LDL particle and showed receptor-mediated toxicity in vitro as judged from the difference in growth inhibitory effect on normal and mutant (LDL-receptor-negative) cultured Chinese hamster ovary cells. However, cellular drug uptake did not exclusively occur by the receptor pathway since mutant cells were also affected to some extent. The LDL part of the complex had the same plasma clearance and organ distribution as native LDL after i.v. injection in mice and rabbits. Therapeutic effects were observed when Balb-C mice with experimental leukaemia were treated with the complex. After i.p. administration to mice with i.p. leukaemia median survival time was prolonged 2.5-fold and 40% became long time survivors. The effect was weaker (42% increase in life span) after i.v. injections of the complex to mice with i.v. leukaemia.
Alkylating Agents↗
Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy.
The success of cancer chemotherapy is dependent on the possibility to utilize biological differences between malignant and normal cells to selectively destroy the tumor cells. One such difference may be that of receptor-mediated cellular uptake of low density lipoproteins (LDLs). Previous studies have shown that leukemic cells from patients with acute myelogenous leukemia have elevated receptor-mediated uptake and degradation rates of plasma LDL in vitro compared to normal white blood and bone marrow cells, and that plasma cholesterol levels at diagnosis are inversely correlated with the LDL receptor activity of the malignant cells. An important question is whether the uptake of LDL by the leukemic cells is also increased in vivo. To evaluate the in vivo uptake of LDL, 11 adult patients with newly diagnosed acute myelogenous leukemia received an i.v. injection of [14C]-sucrose-labeled LDL. On degradation of [14C]sucrose-LDL, the radiolabeled sucrose moiety is known to remain trapped in the lysosomal compartment of the cells. After injection, radioactivity accumulated progressively for at least 12 hr in the leukemic cells. The uptake of radioactivity in vivo correlated with the rate of receptor-mediated degradation of 125I-labeled LDL by the leukemic cells assayed in vitro (r = +0.88, P less than 0.001). An inverse correlation between plasma LDL cholesterol concentrations and the in vivo cellular uptake of [14C]sucrose-LDL in whole blood (r = -0.76, P less than 0.01) indicates that the hypocholesterolemia is due to elevated LDL uptake by the leukemic cells. Postmortem biopsies from virtually all tissues were obtained from one patient, and the distribution of radioactivity revealed that the liver and bone marrow had accumulated most radioactivity; the adrenals had the highest uptake of label per gram of tissue weight. The results indicate that LDL may be used as a carrier targeting lipophilic cytotoxic drugs to leukemic cells.
Adult↗
Determination of plasma azathioprine and 6-mercaptopurine in patients with rheumatoid arthritis treated with oral azathioprine.
Two specific high-performance liquid chromatography methods for determining plasma concentrations of azathioprine and 6-mercaptopurine after oral administration of azathioprine are presented. It was shown that azathioprine is unstable in the blood samples unless immediately cooled in ice water. The 2-amino analog, guaneran, was used as internal standard for azathioprine, which was extracted from plasma with ethylacetate. A Nucleosil C18 column was used for the separation. The detection limit was 6 nM. For quantification of 6-mercaptopurine, 6-thioguanine was used as internal standard. Plasma was deproteinized with HClO4 and the sample was purified on mercurial cellulose. A Beckman ODS column was used and the detection limit was 5 nM. Pharmacokinetic data from two patients are presented. Unchanged azathioprine was seen until 6 h after an oral dose of 32 mg/m2.
Administration, Oral↗
Selective loss of N-methyl-D-aspartate-sensitive L-[3H]glutamate binding sites in rat brain following portacaval anastomosis.
Excitatory amino acids have been implicated in the pathogenesis of hepatic encephalopathy. In the present study, kainate, quisqualate and N-methyl-D-aspartate (NMDA) subclasses of L-glutamate receptors were measured in adult rat brain by quantitative receptor autoradiography following surgical construction of an end-to-side portacaval anastomosis (PCA). PCA resulted in sustained hyperammonemia and decreased binding of L-glutamate to the NMDA receptor when compared to sham-operated controls. Decreases in binding ranged from 17 to 39% in several regions of cerebral cortex, hippocampus, striatum, and thalamus. Binding to quisqualate and kainate receptor subtypes was not altered. PCA leads to astrocytic changes in brain but does not result in any measurable loss of neuronal integrity. It is therefore proposed that decreased glutamate binding to the NMDA receptor following PCA results from increased extracellular glutamate caused by decreased reuptake into perineuronal astrocytes and a compensatory down-regulation of these receptors. Such changes could be of pathophysiological significance in hepatic encephalopathy.
Ammonia↗
Current status of epirubicin (Farmorubicin) in the treatment of solid tumours.
Epirubicin (Farmorubicin) is a drug of significant interest in the treatment of a variety of solid tumours and a comprehensive review of reported investigations is given. From experimental and clinical studies it appears that in general doxorubicin and epirubicin exhibit no qualitative, but only some quantitative, differences. Thus, the pharmacokinetic and pharmacodynamic characteristics of the two drugs are essentially similar, as are the tumour spectrum and the level of their clinical efficacies. To achieve haematological equitoxicity of the two drugs the dose of epirubicin should be approximately 20% higher than that of doxorubicin, giving rise to a higher cumulative dose of epirubicin. On the other hand, epirubicin is significantly less cardiotoxic than doxorubicin. Thus, the recommended cumulative dose of doxorubicin is 500 mg/m2 and the corresponding figure for epirubicin is 1,000 mg/m2. For either drug a number of questions are still left open, the most important of which include the questions about optimal treatment schedules and the existence of a clinical relevant dose/efficacy relationship.
Antineoplastic Combined Chemotherapy Protocols↗