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Biomedical subjects

H Qu

Publications and source records attributed to H Qu.

At least 37 records · Page 2Linked to original sources

Amino acid neurotransmitter metabolism in neurones and glia following kainate injection in rats.

Limbic seizure was induced in rats by intraperitoneal injection of the glutamate receptor agonist kainic acid. After 14 days [1-13C]glucose and [1,2-13C]acetate were injected subcutaneously and the rats killed 15 min later. Analysis of brain extracts was performed using 13C-magnetic resonance spectroscopy and high performance liquid chromatography. No significant differences between the two groups of rats were found for label concentration in blood or total metabolite tissue levels. Only astrocytes are able to utilize acetate as a substrate, whereas glucose is thought to be metabolized predominantly in the neuronal tricarboxylic acid cycle. Thus information about neuronal and astrocytic metabolism could be obtained in the same animal. A significant increase in label derived from [1-13C]glucose was observed in metabolites such as glutamate, gamma-aminobutyric acid, aspartate, and succinate (all of which are mainly labelled in neurones). The increased labelling of glutamine in epileptic rats might be due to transfer of labelled glutamate from neurones to astrocytes. Astrocytic metabolism of acetate and transfer of glutamine to neurones were not affected. The results suggest that increased neuronal activity 2 weeks following epileptic seizures produces increased amino acid turnover in neurones. Changes in astrocytic metabolism were not detected.

Animals↗

In vivo effects of adenosine A1 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13C NMR spectroscopy.

Adenosine is a neuromodulator, and it has been suggested that cerebral acetate metabolism induces adenosine formation. In the present study the effects that acetate has on cerebral intermediary metabolism, compared with those of glucose, were studied using the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Fasted rats received an intravenous injection of CCPA, DPCPX, or vehicle. Fifteen minutes later either [1,2-13C]acetate or [1-13C]glucose was given intraperitoneally; after another 30 min the rats were decapitated. Cortical extracts were analyzed with 13C NMR spectroscopy and HPLC analysis. DPCPX affected neuronal and astrocytic metabolism. De novo synthesis of GABA from neuronal and astrocytic precursors was significantly reduced. De novo syntheses of glutamate and aspartate were at control levels, but their degradation was significantly elevated. In glutamine the anaplerotic activity and the amount of label in the position representing the second turn in the tricarboxylic acid cycle were significantly increased, suggesting elevated metabolic activity in astrocytes. CCPA did not influence GABA, aspartate, or glutamine synthesis. In glutamate the contribution from the astrocytic anaplerotic pathway was significantly decreased. In the present study the findings in the [1,2-13C]acetate and [1-13C]glucose control, CCPA, and DPCPX groups were complementary, and no adenosine A1 agonist effects arising from cerebral acetate metabolism were detected.

Acetates↗

Decreased glutamate metabolism in cultured astrocytes in the presence of thiopental.

The effect of thiopental on glutamate metabolism was studied by 13C magnetic resonance spectroscopy. Cerebral cortical astrocytes were incubated with 0.5 mM [U-13C]glutamate for 2 hr in the presence of 0.5 or 1 mM thiopental. Labeled glutamate, glutamine, aspartate, and glutathione were observed in cell extracts, and glutamine, aspartate, and lactate in the medium. Not only present in the medium was uniformly labeled glutamate, but also glutamate derived from the tricarboxylic acid (TCA) cycle, and thus glutamate release could be detected. The amounts of [U-13C]glutamate and unlabeled glucose taken up by astrocytes were unchanged in the presence of 0.5 mM thiopental and decreased to about 50% and 80%, respectively when the concentration was increased to 1 mM. The amounts of most metabolites synthesized from [U-13C]glutamate were unchanged in the presence of 0.5 mM thiopental, but decreased [U-13C]glutamine, [U-13C]aspartate, and [U-13C]lactate were observed in the 1 mM group. Surprisingly, the amounts of [1,2,3-13C]glutamate, [2,3-13C]aspartate, and [3,4-13C]aspartate (2nd turn via the TCA cycle) were unchanged. However, this was not the case for [1,2-13C]lactate and [2,3-13C]lactate. Such variations indicate cellular compartmentation, possibly caused by a heterogeneous glutamate concentration within the cells affecting TCA cycle turnover rates differently.

Anesthetics, Intravenous↗

Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells.

Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.

Adult↗

In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat.

Astrocytes play a pivotal role in cerebral glutamate homeostasis. After 90 minutes of middle cerebral artery occlusion in the rat, the changes induced in neuronal and astrocytic metabolism and in the neuronal-astrocytic interactions were studied by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy and HPLC analysis of amino acids of the lateral caudoputamen and lower parietal cortex, representing the putative ischemic core, and the upper frontoparietal cortex, corresponding to the putative penumbra. In the putative ischemic core, evidence of compromised de novo glutamate synthesis located specifically in the glutamatergic neurons was detected, and a larger proportion of glutamate was derived from astrocytic glutamine. In the same region, pyruvate carboxylase activity, representing the anaplerotic pathway in the brain and exclusively located in astrocytes, was abolished. However, astrocytic glutamate uptake and conversion to glutamine took place, and cycling of intermediates in the astrocytic tricarboxylic acid cycle was elevated. In the putative penumbra, glutamate synthesis was improved compared with the ischemic core, the difference appeared to be brought on by better neuronal de novo glutamate synthesis, combined with normal levels of glutamate formed from astrocytic glutamine. In both ischemic regions, gamma-aminobutyric acid synthesis directly from glucose was reduced to about half, indicating impaired pyruvate dehydrogenase activity; still, gamma-aminobutyric acid reuptake and cycling was increased. The results obtained in the current study demonstrate that by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy, specific metabolic alterations in small regions within the rat brain suffering a focal ischemic lesion can be studied.

Acetates↗

In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.

Pyruvate recycling is a well established pathway in the liver, but in the brain, the cellular localization of pyruvate recycling remains controversial and its physiological significance is unknown. In cultured cortical astrocytes, pyruvate formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C-3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling in astrocytes. This finding is in agreement with previous studies of astrocytic cultures, in which pyruvate recycling has been described from [U-13C]glutamine, in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in brain was studied in fasted rats receiving either an intraperitoneal or a subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later. Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H- and 13C-NMR spectroscopy, and showed a significantly larger amount of [1, 2-13C]acetate in the intraperitoneal group compared to the subcutaneous group. Furthermore, a small amount of label was detected in glucose in both groups. In the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less enriched than plasma glucose, which might have been the precursor. In the intraperitoneally injected rats, however, pyruvate formation from [1, 2-13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine compared to the subcutaneous group, probably resulting from the significantly higher [1, 2-13C]acetate concentration in brain and plasma.

Acetates↗

[Endovascular treatment of intracranial aneurysms with GDC: report of 8 cases].

OBJECTIVE: To assess the usefulness and practical experience in intracranial aneurysm embolization with guglielmi detachable coil (GDC) applied firstly in China. METHOD: Under general anesthesia and systematic anticoagulation, eight cases of intracranial aneurysms were embolized with GDC which was introduced by tracker micro-catheter, combined remodeling technique (RT) if necessary. RESULT: 100% occlusion was achieved in 5 cases, 95% in 2 and 90% in 1, without any complication. Among these cases, 4 failed in the previous attempts of endovascular treatment with mechanical detachable system (MDS), because MDS could not be safely and totally placed inside the aneurysms and Mag 3F/2F micro-catheter could not be navigated into the aneurysms. CONCLUSION: Embolization of intracranial aneurysms with GDC is safe, effective and reliable, and it may offer the cure opportunity to those enearysms which are very dangerous to embolize or can not be embolized with MDS.

Adult↗

[Surgical treatment of spinal dural arteriovenous fistulas].

OBJECTIVE: To discuss the operation modalities of spinal dural arteriovenous fistulae (SDAVFs) and treatment with anticoagulant agents after surgery. METHOD: The medical records, radiographic studies and operations of 23 patients with SDAVFs were reviewed. Laminectomy was performed at the level of the arterialized venous entry into the subarachnoid space in 18 patients with thoracic and lumbar lever AVFs, followed by coagulation, clipping and division of the vein. In 14 of 18 patients, the arteriovenous nidus in the dura was identified and obliterated by coagulation. The draining veins were interrupted at L(5) - S(1) level in 5 patients with sacral AVFs. Anticoagulant treatment was given in 13 patients. RESULT: Outcome was good in 20 patients and 2 of the 20 had transient postoperative neurological deterioration that reversed by anticoagulant agents. No changes were seen in 2 patients except one deteriorated. CONCLUSION: Surgical interruption of arterialized radicular-medullary draining vein of SDAVFs provides lasting occlusion of the fistula, and postoperative anticoagulant therapy can prevent thrombosis of the coronal venous plexus.

Adult↗

A patient-specific algorithm for the detection of seizure onset in long-term EEG monitoring: possible use as a warning device.

During long-term electroencephalogram (EEG) monitoring of epileptic patients, a seizure warning system would allow patients and observers to take appropriate precautions. It would also allow observers to interact with patients early during the seizure, thus revealing clinically useful information. We designed patient-specific classifiers to detect seizure onsets. After a seizure and some nonseizure data are recorded in a patient, they are used to train a classifier. In subsequent monitoring sessions, EEG patterns have to pass this classifier to determine if a seizure onset occurs. If it does, an alarm is triggered. Extreme care has been taken to ensure a low false-alarm rate, since a high false-alarm rate would render the system ineffective. Features were extracted from the time and frequency domains and a modified nearest-neighbor (NN) classifier was used. The system reached an onset detection rate of 100% with an average delay of 9.35 a after onset. The average false-alarm rate was only 0.02/h. The method was evaluated in 12 patients with a total of 47 seizures. Results indicate that the system is effective and reasonably reliable. Computation load has been kept to a minimum so that real-time processing is possible.

Algorithms↗

Intrachondral microvasculature in the human fetal talus.

The intrachondral microvasculature of the growing talus of human was studied in 16 fetuses aged from 15 to 44 weeks of gestation, using interrupted serial sections and vascular injection of ink. The cartilage model of the talus was shown to be well vascularized throughout by cartilage canals. The cartilage canal contained blood vessels and connective tissue, with vessels originating from the perichondrial vessels. They were covered by a thick connective tissue wall that was continuous with the perichondrium. The functions of the cartilage canals were mainly to nourish the large masses of cartilage and to supply osteogenic tissue, which initiates the primary ossification center. As in the adult, the fetal talus was supplied with four to five main branches originating from the sinus tarsi and the tarsal canal; there were no anastomoses between the vessels of the adjacent cartilage canals and between the branches within the cartilage canal. This type of microvasculature is vulnerable to injury and, if impaired, may cause serious complications.

Blood Vessels↗

Singles transmission in volume-imaging PET with a 137Cs source.

The feasibility of a new method of attenuation correction in PET has been investigated, using a single-photon emitter for the transmission scan. The transmission scan is predicted to be more than a factor of ten faster with the singles method than the standard coincidence method, for comparable statistics. Thus, a transmission scan be completed in 1-2 min, rather than 10-20 min, as is common practice with the coincidence method. In addition, a potential advantage of using the single-photon source 137Cs, which has an energy of 662 keV, is that postinjection transmission studies can be performed using energy discrimination to separate the transmission from the emission data at 511 keV. In order to compensate for the energy difference of the attenuation coefficients at 662 keV compared to 511 keV, the transmission images are segmented into two compartments, tissue and lung, and known values (for 511 keV) of attenuation are inserted into these compartments. This technique also compensates for the higher amount of scatter present with the singles method, since it is not possible to use a position gate (based on collinearity of the source and two detector positions) as is commonly done with a positron-emitting source. We have demonstrated, with experimental phantom studies, that the singles transmission method combined with segmentation gives results equivalent both qualitatively and quantitatively to the coincidence method, but requires significantly less time.

Biophysical Phenomena↗

Ossification processes and perichondral ossification groove of Ranvier: a morphological study in developing human calcaneus and talus.

In this histologic-radiologic investigation of 32 feet of 16 fetuses and newborns ranging in age from 15 to 44 weeks, two types of ossification, i.e., endochondral ossification through primary ossification center and intramembraneous ossification through periosteal bone formation (PBF), were found to coexist in both calcaneus and talus. In addition, Ranvier's grooves (RG), or perichondral ossification groove, also was observed as a shallow, saucer-like or semicircular structure. As with PBFs, there are three and two RGs in the calcaneus and talus, respectively. RG and PBF appeared in time order and were located regularly in the concave areas of the adult calcaneus and talus. The findings support the hypothesis that one function of PBF and RG is to limit the growth of the calcaneus and talus. Thus, they are responsible for the irregular contour of the calcaneus and talus.

Calcaneus↗

A seizure warning system for long-term epilepsy monitoring.

We developed a system to provide a warning early in the development of a seizure with a reasonably low false alarm rate. Such a warning will improve the close observation of seizures and interaction between observers and patients early in the seizure, even in seizures having no obvious clinical manifestation. The system relies on the availability of the EEG recording of one sample seizure, which is used as a template for subsequent detection. We evaluated the performance in 24 seizure types from scalp and intracerebral recordings. It yielded a 100% detection rate and a false alarm rate averaging one false alarm every 5 hours. The warning signal was given, on average, 9.6 seconds after EEG seizure onset. The system will be useful in improving the clinical observation of seizures and may allow ictal SPECT scans to be more widely performed.

Electroencephalography↗

Improvement in seizure detection performance by automatic adaptation to the EEG of each patient.

An important problem in the use of automatic seizure detection during long-term epilepsy monitoring is that false detections can be very frequent, often because a paroxysmal but non-epileptiform pattern occurs repeatedly in a particular patient. We therefore introduce a method to reduce such patient-specific false seizure detections. The program "learns" about the false detections occurring in the first day of a prolonged monitoring session and attempts to eliminate similar patterns occurring during the remainder of the session. This method was evaluated in 20 patients having particularly high false detection rates. Seventy EEG sessions from 10 patients with scalp electrodes and 64 sessions from 10 patients with depth electrodes, covering a total of 2600 h were used in the evaluation. False detections were reduced by 61% (50% in scalp recordings and 71% in depth recordings), with only a 5% probability of losing true seizures. The average false detection rate in these patients fell from 3.25/h to 1.26/h. This significant reduction in false detections could also lead to lower detection thresholds and consequently to the detection of more true seizures.

Automation↗

[A histological study on peripheral iris in primary angle closure glaucoma].

Iris specimens obtained during the peripheral iridectomy in 12 cases (18 eyes) of primary angle closure glaucoma were studied histologically. The iris specimens taken during the senile cataract extraction in otherwise normal eyes were used as controls. The remarkable differences of the two groups are the changes of the quality and quantity of the mitochondria in the cells of iris tissue. The changes in primary glaucoma, especially in the intermittent stage of the angle closure glaucoma, were found in the mitochondria of the cells.

Glaucoma, Angle-Closure↗