Long term care in later life. Best providers should win contracts irrespective of their ownership.
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Aged↗
Biomedical subjects
B Hassel
Publications and source records attributed to B Hassel.
Metabolic differences between primary cultures of astrocytes and neurons from cerebellum and cerebral cortex. Effects of fluorocitrate.
Astrocytes and neurons cultured from mouse cerebellum and cerebral cortex were analyzed with respect to content and synthesis of amino acids as well as export of metabolites to the culture medium and the response to fluorocitrate, an inhibitor of aconitase. The intracellular levels of amino acids were similar in the two astrocytic populations. The release of citrate, lactate and glutamine, however, was markedly higher from cerebellar than from cortical astrocytes. Neurons contained higher levels of glutamate, aspartate and GABA than astrocytic cultures. Cortical neurons were especially high in GABA and aspartate, and the level of aspartate increased specifically when the extracellular level of glutamine was elevated. Fluorocitrate inhibited the TCA cycle in the astrocytes, but was less effective in cerebellar neurons. Whereas neurons responded to fluorocitrate with an increase in the formation of lactate, reflecting glycolysis, astrocytes decreased the formation of lactate in the presence of fluorocitrate, indicating that astrocytes to a high degree synthesize pyruvate and hence lactate from TCA cycle intermediates.
Amino Acids↗
Skeletal maturation evaluation using cervical vertebrae.
Lateral cephalometric and left hand-wrist radiographs from the Bolton-Brush Growth Center at Case Western Reserve University were reviewed a posteriori to develop a cervical vertebrae maturation index (CVMI). By using the lateral profiles of the second, third and fourth cervical vertebrae, it was possible to develop a reliable ranking of patients according to the potential for future adolescent growth potential.
Adolescent↗
Glial-neuronal interactions as studied by cerebral metabolism of [2-13C]acetate and [1-13C]glucose: an ex vivo 13C NMR spectroscopic study.
Mice were injected intravenously with [2-13C]-acetate or [1-13C]glucose and killed after 5, 15, or 30 min. Another group of animals was injected three times subcutaneously during 30 min with [2-13C]acetate to achieve a steady-state-like situation. Brain extracts were analyzed by 13C NMR spectroscopy, and the percent enrichment of various carbon positions was calculated for amino acids, lactate, and glucose. Results obtained with [2-13C]acetate, which is metabolized by glia and not by neurons, showed that glutamine originated from a glial tricarboxylic acid cycle (TCA cycle) that loses 65% of its intermediates per turn of the cycle. This TCA cycle was associated with pyruvate carboxylation, which may replenish virtually all of this loss, as seen from the labeling of glutamine from [1-13C]glucose. From the C-3/C-4 labeling ratios in glutamine and glutamate and from the corresponding C-3/C-2 labeling ratio in GABA obtained with [2-13C]acetate, it was concluded that the carbon skeleton of glutamine to some extent was passed through TCA cycles before glutamate and GABA were formed. Thus, astrocytically derived glutamine is not only a precursor for transmitter amino acids but is also an energy substrate for neurons in vivo. Furthermore, the neuronal TCA cycles may be control points in the synthesis of transmitter amino acids. Injection of [2-13C]acetate led to a higher 13C enrichment of the C-2 in glutamate and of the corresponding C-4 in GABA than in the C-3 of either compound. This could reflect cleavage of [2-13C]-citrate and formation of [3-13C]oxaloacetate and acetyl-Coa, i.e., the first step in fatty acid synthesis. [3-13C]-Oxaloacetate would, after entry into a TCA cycle, give the observed labeling of glutamate and GABA.
Acetates↗
Selective inhibition of the tricarboxylic acid cycle of GABAergic neurons with 3-nitropropionic acid in vivo.
The effects of 3-nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase, on cerebral metabolism were investigated in mice by NMR spectroscopy. 3-NPA, 180 mg/kg, caused a dramatic buildup of succinate. Succinate was labeled 5.5 times better from [1-(13)C]glucose than from [2-(13)C]acetate, showing a predominantly neuronal accumulation. [1-(13)C]Glucose labeled GABA in the C-2 position only, compatible with inhibition of the tricarboxylic acid (TCA) cycle associated with GABA formation, at the level of succinate dehydrogenase. Aspartate was not labeled by [1-(13)C]glucose in 3-NPA-intoxicated animals. In contrast, [1-(13)C]glucose labeled glutamate in the C-2, C-3, and C-4 positions showing uninhibited cycling of label in the TCA cycle associated with the large, neuronal pool of glutamate. The labeling of glutamine, and hence GABA, from [2-(13)C]acetate showed that the TCA cycle of glial cells was unaffected by 3-NPA and that transfer of glutamine from glia to neurons took place during 3-NPA intoxication. The high 13C enrichment of the C-2 position of glutamine from [1-(13)C]glucose showed that pyruvate carboxylation was active in glia during 3-NPA intoxication. These findings suggest that 3-NPA in the initial phase of intoxication fairly selectively inhibited the TCA cycle of GABAergic neurons; whereas the TCA cycle of glia remained uninhibited as did the TCA cycle associated with the large neuronal pool of glutamate, which includes glutamatergic neurons. This may help explain why the caudoputamen, which is especially rich in GABAergic neurons, selectively undergoes degeneration both in humans and animals intoxicated with 3-NPA.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids?
Cerebral formation of lactate via the tricarboxylic acid (TCA) cycle was investigated through the labeling of lactate from [2-13C]acetate and [1-13C]glucose as shown by 13C NMR spectroscopy. In fasted mice that had received [2-13C]acetate intravenously, brain lactate C-2 and C-3 were labeled at 5, 15, and 30 min, reflecting formation of pyruvate and hence lactate from TCA cycle intermediates. In contrast, [1-13C]glucose strongly labeled lactate C-3, reflecting glycolysis, whereas lactate C-2 was weakly labeled only at 15 min. These data show that formation of pyruvate, and hence lactate, from TCA cycle intermediates took place predominantly in the acetate-metabolizing compartment, i.e., glia. The enrichment of total brain lactate from [2-13C]acetate reached approximately 1% in both the C-2 and the C-3 position in fasted mice. It was calculated that this could account for 20% of the lactate formed in the glial compartment. In fasted mice, there was no significant difference between the labeling of lactate C-2 and C-3 from [2-13C]acetate, whereas in fed mice, lactate C-3 was more highly labeled than the C-2, reflecting adaptive metabolic changes in glia in response to the nutritional state of the animal. It is hypothesized that conversion of TCA cycle intermediates into pyruvate and lactate may be operative in the glial metabolism of extracellular glutamate and GABA in vivo. Given the vasodilating effect of lactate on cerebral vessels, which are ensheathed by astrocytic processes, conversion of glutamate and GABA into lactate could be one mechanism mediating increases in cerebral blood flow during nervous activity.
Amino Acids↗
[Acute hypothermia and adverse effects on the central nervous system during erythromycin therapy].
Acute hypothermia and central nervous symptoms were observed in a 1 1/2 year-old child treated with erythromycin. The symptoms were mild hypothermia, ataxia, somnolence and apparent fatigue. Withdrawal of erythromycin led to reversal of the symptoms. Such side effects of antibiotics may be misinterpreted as involvement of the central nervous system in the infection for which the drug was given.
Acute Disease↗
Neurotoxicity of albumin in vivo.
The neurotoxicity of albumin was studied in the rat. Solutions of rat albumin (3, 10 and 30 mg/ml) essentially free of fatty acids and globulins were injected into one neostriatum, physiological saline into the other. Injections were also performed with sodium glutamate (10 and 30 mM). Both albumin and glutamate produced lesions in a concentration-dependent manner. Thus 3, 10 and 30 mg/ml albumin produced lesions in excess of saline of 22 +/- 24 microns3, 67 +/- 25 microns3 and 170 +/- 44 microns3, (P = 0.82, 0.03 and 0.0005, respectively). 10 and 30 mM sodium glutamate caused lesions of 45 +/- 14 microns3 and 315 +/- 56 microns3 in excess of saline (P = 0.04 and 0.0004, respectively). Injection of 10 mg/ml albumin together with 10 mM sodium glutamate caused lesions of 70 +/- 11 microns3 in excess of saline (P = 0.005). This was not significantly different from the lesions caused by any of the two substances alone. Thus no potentiating effect of one substance on the toxicity of the other was seen in this study. The neurotoxicity of albumin could be of importance in disease states which are accompanied by leakiness of the blood-brain barrier.
Animals↗
NMR spectroscopy of cultured astrocytes: effects of glutamine and the gliotoxin fluorocitrate.
Glial synthesis of glutamine, citrate, and other carbon skeletons, as well as metabolic effects of the gliotoxin fluorocitrate, were studied in cultured astrocytes with 13C and 31P NMR spectroscopy. [2-13C]Acetate and [1-13C]glucose were used as labeled precursors. In some experiments glutamine (2.5 mM) was added to the culture medium. Fluorocitrate (20 microM) inhibited the tricarboxylic acid (TCA) cycle without affecting the level of ATP. The net export of glutamine was reduced significantly, and that of citrate increased similarly, consistent with an inhibition of aconitase. Fluorocitrate (100 microM) inhibited TCA cycle activity even more and (without addition of glutamine) caused a 40% reduction in the level of ATP. In the presence of 2.5 mM glutamine, 100 microM fluorocitrate did not affect ATP levels, although glutamine synthesis was nearly fully blocked. The consumption of the added glutamine increased with increasing concentrations of fluorocitrate, whereas the consumption of glucose decreased. This shows that glutamine fed into the TCA cycle, substituting for glucose as an energy substrate. These findings may explain how fluorocitrate selectively lowers the level of glutamine and inhibits glutamine formation in the brain in vivo, viz., not by depleting glial cells of ATP, but by causing a rerouting of 2-oxoglutarate from glutamine synthesis into the TCA cycle during inhibition of aconitase. Analysis of the 13C labeling of the C-2 versus the C-4 positions in glutamine obtained with [2-13C]acetate revealed that 57% of the TCA cycle intermediates were lost per turn of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetates↗
Early entry of plasma proteins into damaged neurons in brain infarcts. An immunohistochemical study on experimental animals.
Entry of plasma proteins into damaged neurons has previously been demonstrated in various pathological conditions, but little is known about brain infarcts in this respect. In the present study, focal ischemic lesions were produced in rats by permanent occlusion of the middle cerebral artery (MCA). The animals were killed from 1 to 48 h postlesion. Leakage of plasma proteins across the blood-brain barrier into the infarcted area was visualized with immunostaining 2-3 h after the occlusion. This is earlier than in most previous reports. Entry of plasma proteins into ischemic neurons was seen 3 h after permanent occlusion of the MCA, while reliable changes were not seen until 12-24 h in sections stained with hematoxylin and eosin (H & E). Ischemic neurons stained for plasma proteins irrespective of their morphological appearance. Even cells that appeared normal with H & E staining were positively labeled. The technique may be used to diagnose very early ischemic lesions.
Animals↗
Treatment of biliary colic with nitroglycerin.
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Adult↗
NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: evidence for mitochondrial heterogeneity.
Neocortical astrocytes were incubated with 13C-labeled substrates to determine metabolic pathways. 13C NMR spectroscopy was used to analyze 13C incorporation into glutamine and citrate from the different precursors--[1-13C]glucose or [2-13C]acetate. When glucose was the labeling substrate, incorporation due to pyruvate carboxylation should be observed in the C-2 position in glutamine and the C-4 position in citrate. A large incorporation due to pyruvate carboxylation was observed in glutamine in the C-2 and C-3 positions, but not in citrate. When acetate was the precursor, the labeling ratios in the C-2/C-4 positions in glutamine and in the equivalent positions in citrate were 0.27 and 0.11, respectively. Moreover, acetate labeled lactate in the C-2 position much less than did glucose. Altogether, these observations led to the conclusion that glutamine precursors and citrate are either produced in different types of astrocytes or in different tricarboxylic acid cycles, situated in functionally different mitochondria in the same cell, and that in all likelihood pyruvate carboxylase is expressed differently in these mitochondria.
Acetates↗
Acute hypothermia due to penicillin.
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Acute Disease↗
Selective inhibition of glial cell metabolism in vivo by fluorocitrate.
The effect of fluorocitrate on glial and neuronal amino acid metabolism was studied. One nmol of fluorocitrate administered intrastriatally in the rat caused a 95% reduction of glutamine formation from [14C]acetate, a substrate which enters the glial cells selectively. The metabolism of [14C]glucose which enters neurons, was unaffected by fluorocitrate treatment except for the glutamine formation. This is evidence that fluorocitrate is a selective inhibitor of the glial Krebs' cycle. [14C]Citrate and 2-oxoglutarate labelled amino acids in a manner similar to [14C]acetate, which shows that these substrates are taken up and metabolized by glial cells. Differences in the labelling of gamma-aminobutyric acid (GABA) from [14C]acetate and citrate suggest that astrocytes associated with GABAergic and glutamatergic nerve terminals may differ in their preference for amino acid precursors.
Acetates↗
Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro.
Notch locus EGF-like element mutations spl, altering eye development, and AxE2, affecting wing and sensilla development, are modified by mutations at Delta. It is shown that two allele-specific suppressors of spl involve single amino acid substitutions in the 4th (Dlsup5) and 9th (Dlsup4) EGF-like elements of the Delta protein. Cultured cells producing spl or AxE2 aggregate with cells producing wild-type Delta or Dlsup5 protein, and Dlsup5-producing cells adhere to cells producing wild-type Notch protein. However, spl,AxE2, and Dlsup5 are each defective in promoting these cell affinities, as none of the mutant proteins can compete with the corresponding wild-type proteins for formation of cell aggregates. Thus, widely separated EGF-like elements of Notch and Delta appear to participate in functional molecular interactions between the proteins. Dlsup5 does not improve adhesiveness of spl in vitro, so suppression in vivo may involve altered developmental signaling by spl-Dlsup5 complexes, rather than modified cell adhesion.
Amino Acid Sequence↗
Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily.
The chick axon-associated surface glycoprotein neurofascin is implicated in axonal growth and fasciculation as revealed by antibody perturbation experiments. Here we report the complete cDNA sequence of neurofascin. It is composed of four structural elements: At the NH2 terminus neurofascin contains six Ig-like motifs of the C2 subcategory followed by four fibronectin type III (FNIII)-related repeats. Between the FNIII-like repeats and the plasma membrane spanning region neurofascin contains a domain 75-amino acid residues-long rich in proline, alanine and threonine which might be the target of extensive O-linked glycosylation. A transmembrane segment is followed by a 113-amino acid residues-long cytoplasmic domain. Sequence comparisons indicate that neurofascin is most closely related to chick Nr-CAM and forms with L1 (Ng-CAM) and Nr-CAM a subgroup within the vertebrate Ig superfamily. Sequencing of several overlapping cDNA probes reveals interesting heterogeneities throughout the neurofascin polypeptide. Genomic Southern blots analyzed with neurofascin cDNA clones suggest that neurofascin is encoded by a single gene and its pre-mRNA might be therefore alternatively spliced. Northern blot analysis with domain specific probes showed that neurofascin mRNAs of about 8.5 kb are expressed throughout development in embryonic brain but not in liver. Isolation of neurofascin by immunoaffinity chromatography results in several molecular mass components. To analyze their origin the amino-terminal sequences of several neurofascin components were determined. The NH2-terminal sequences of the 185, 160, and 110-135 kD components are all the same as the NH2 termini predicted by the cDNA sequence, whereas the other neurofascin components start with a sequence found in a putative alternatively spliced segment between the Ig- and FNIII-like part indicating that they are derived by proteolytic cleavage. A combination of enzymatic and chemical deglycosylation procedures and the analysis of peanut lectin binding reveals O- and N-linked carbohydrates on neurofascin components which might generate additional heterogeneity.
3T3 Cells↗
Calcifying aponeurotic fibroma. A case of multiple primary tumours. Case report.
A 20 year old man had had three subcutaneous tumours on his left forefinger for 15 years. After operation they were found to be infiltrating into the surrounding tissue, and histological examination showed them to be calcifying aponeurotic fibromas. To the knowledge of the author this is the first reported case of multiple primary tumours of this kind.
Adult↗
Fulminant myasthenia gravis and polymyositis after thymectomy for thymoma.
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Adult↗