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Biomedical subjects

E Kang

Publications and source records attributed to E Kang.

At least 19 recordsLinked to original sources

Enhancing forest carbon sequestration in China: toward an integration of scientific and socio-economic perspectives.

This article serves as an introduction to this special issue, "China's Forest Carbon Sequestration", representing major results of a project sponsored by the Canadian International Development Agency and the Chinese Academy of Sciences. China occupies a pivotal position globally as a principle emitter of carbon dioxide, as host to some of the world's largest reforestation efforts, and as a key player in international negotiations aimed at reducing global greenhouse gas emission. The goals of this project are to develop remote sensing approaches for quantifying forest carbon balance in China in a transparent manner, and information and tools to support land-use decisions for enhanced carbon sequestration (CS) that are science based and economically and socially viable. The project consists of three components: (i) remote sensing and carbon modeling, (ii) forest and soil assessment, and (iii) integrated assessment of the socio-economic implications of CS via forest management. Articles included in this special issue are highlights of the results of each of these components.

Air Pollution↗

Vegetation and carbon sequestration and their relation to water resources in an inland river basin of Northwest China.

In the Heihe River Basin in the arid inland area of northwest China, the distribution of water resources in vegetation landscape zones controls the ecosystems. The carbon sequestration capacity of vegetation is analyzed in relation to water resources and vegetation growing conditions. During the last 20 years, the vegetation ecosystems have degenerated in the Heihe River Basin. Simulation using the C-FIX model indicates that, at present, the total amount of NPP of vegetation accounts for about 18.16 TgC, and the average value is 106 gC/m(2)/yr over the whole basin. NPP has generally the highest value in the upperstream mountain area, middlestream artificial oases area, downstream river bank area, alluvial fan and the terminal lake depression where vegetation grows relatively well. The lowest value is found in the vast downstream desert and Gobi area. Protection of vegetation ecosystems and enhancement of carbon sequestration require such inland river basins as the Heihe River Basin to be brought under management in a comprehensive way, taking water as a key, to carry out a rational and efficient allocation and utilization of water resources.

Altitude↗

Subventricular zone cells remain stable in vitro after brain injury.

Subventricular zone (SVZ) cells emigrate toward brain injury but relatively few survive. Thus, if they are to be used for repair, ex vivo expansion and autologous transplantation of SVZ cells may be necessary. Since it is unclear how brain injury alters SVZ cell culture, we studied neurosphere formation, differentiation, and migration, after cortical lesions. The number of neurosphere forming cells from lesioned mice was comparable to controls. Also, the proportion of astrocytes and neurons generated in vitro remained unchanged after cortical lesions. Cell emigration from neurospheres was characterized by increased cell-cell contact after injury in adults and neonates. However, neither molecules implicated in SVZ migration nor the extent of migration changed after injury. Thus, neurospheres can be successfully cultured after extensive brain damage, and they are remarkably stable in vitro, suggesting suitability for ex vivo expansion and autologous transplantation.

Animals↗

Altered neural circuit for working memory before and after symptom provocation in patients with obsessive-compulsive disorder.

OBJECTIVE: The authors compared the neural circuits recruited for working memory (WM) in obsessive-compulsive disorder (OCD) patients both at a neutral state and at a symptom provoked state. METHOD: Twelve OCD patients, and 12 age-, and sex-matched healthy subjects underwent [(15)O]H(2)O positron emission tomography (PET) scanning, while performing WM task. In the patients, the tasks were performed both in the neutral and in the symptom provoked states. RESULTS: In the OCD patients, the right caudate and the right superior parietal cortex (rSPC) displayed activations for WM at the neutral state, while the right cingulate cortex and rSPC displayed activations for WM at the symptom provoked state. Path analysis revealed that the activity of the caudate and orbitofrontal cortex was altered according to the interaction between WM and symptom provocation. CONCLUSION: The interaction between symptom provocation and WM occurring in the fronto-striatal system may hold the key to the neurobiology of OCD.

Adult↗

Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients.

The aims of this cross-sectional study were (i) to compare the overall glucose metabolism between early onset and late onset Alzheimer's disease in a large sample of patients; and (ii) to investigate the pattern of glucose metabolism as a function of dementia severity in early onset versus late onset Alzheimer's disease, using a statistical parametric mapping (SPM) analysis. Subjects consisted of four groups: 74 patients with early onset Alzheimer's disease, 46 patients with late onset of the disease, and two control groups age matched to each patient group. All the subjects underwent 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET under the same scanning conditions. Severity of dementia was rated with the Clincial Dementia Rating (CDR). Voxel-based SPM99 was used for statistical analyses. Overall glucose hypometabolism of early onset Alzheimer's disease patients was much greater in magnitude and extent than that of late onset patients, though both groups were similar in dementia severity: the early onset group showed more severe hypometabolism in parietal, frontal and subcortical (basal ganglia and thalamus) areas. When the decline of glucose metabolism was compared as a function of CDR stage, the slope was steeper in early onset than in late onset Alzheimer's disease. The rapid decline occurred at CDR 0.5-1 in the early onset group, whereas similar changes occurred at CDR 2-3 in the late onset group. The greater hypometabolism in early onset than in late onset patients is required to reach the same severity of dementia, probably reflecting greater functional reserve in younger than in older subjects. Alternatively, the metabolic decline curve suggests that the early onset patients may take a more rapid course in the reduction of glucose metabolism than the late onset patients.

Age of Onset↗

Pattern of glucose hypometabolism in frontotemporal dementia with motor neuron disease.

Frontotemporal dementia (FTD) often coexists with motor neuron disease (MND). To characterize glucose hypometabolism in patients with FTD with MND (FTD/MND), the authors compared the glucose metabolism of 8 patients with FTD/MND with that of 29 patients with FTD. All of the patients with FTD/MND showed glucose hypometabolism only in the frontal area, whereas most patients with FTD had hypometabolism in the frontal and temporal areas. FTD/MND also showed a more symmetric pattern of glucose hypometabolism than FTD.

Aged↗

Developmental hemispheric asymmetry of interregional metabolic correlation of the auditory cortex in deaf subjects.

The functional connectivity of the auditory cortex might be altered in deaf subjects due to the loss of auditory input. We studied the developmental changes of functional connectivity of the primary auditory cortex (A1) in deaf children, deaf adults, and normal hearing adults by examining interregional metabolic correlation with (18)F-FDG PET. The mean activity of FDG uptake in the cytoarchitectonically defined A1 region served as a covariate in the interregional and interhemispheric correlation analysis. A1 metabolic rate was correlated with that of the ipsilateral superior temporal lobe in both normal and deaf subjects. This correlated area was larger in deaf children than in deaf or normal hearing adults. Concerning the functional connectivity of A1, a hemispheric asymmetry was found in that the extent of interregional correlation was clearly larger in the right than in the left hemisphere. This asymmetry was particularly pronounced in the younger deaf children. Both extent and asymmetry of the functional connectivity of A1 subsided with age. Contrary to this, a correlation between the left and the right primary auditory cortices was absent in younger deaf children but became apparent as they grew older.

Adolescent↗

In vivo persistence of retrovirally transduced murine long-term repopulating cells is not limited by expression of foreign gene products in the fully or minimally myeloablated setting.

Many nonmalignant hematologic disorders could potentially be treated by genetic correction of as few as 5-10% of target lineage cells. However, immune system clearance of cells expressing gene products perceived as foreign could be limiting. There is evidence that tolerance to foreign proteins can result when myeloablative conditioning is used, but this limits the overall applicability of such techniques. Therefore, we sought to evaluate the engraftment of hematopoietic stem cells carrying a foreign transgene after low-dose irradiation by comparing in vivo survival of murine long-term repopulating cells (LTRC) transduced with either a retroviral vector expressing the bacterial neomycin phosphotransferase gene (neo) or a vector containing neo gene sequences but modified to prevent protein expression (nonexpression). First, marrow cells from congenic donors were transduced with either vector and transplanted into recipients treated with standard dose irradiation of 800 rads. High-level engraftment and gene marking resulted, without differences in the marking levels or pattern of persistence of the cells between cells transduced with either vector. Low-dose irradiation at 100 rads was tested using higher cell doses. Marking levels as high as 10% overall were obtained, again with no differences between mice receiving cells transduced with the neo versus the nonexpression vectors. To investigate a potentially more immunogenic protein, marrow cells were transduced with a vector containing the green fluorescent protein (GFP) gene, and their persistence was studied in recipient mice receiving 100 rads. Stable GFP expression in 5-10% of circulating cells was observed long term. We conclude that even with very low dose conditioning, engraftment by genetically modified LTRC cells at clinically significant levels can be achieved without evidence for clearance of cells known to be expressing immunogenic proteins.

Animals↗

Functional magnetic resonance imaging during pantomiming tool-use gestures.

The purpose of this study was to identify the functional fields activated in relation to gestural movements. Using functional magnetic resonance imaging (fMRI), we mapped brain activity in ten right-handed, normal volunteers during activation and control tasks. The activation condition consisted of pantomiming tool-use gestures with either the left hand or right hand, whereas the control condition comprised repetitive, oppositional movements between thumb and index finger. Activated cortical regions were highly lateralized to the left hemisphere during pantomiming of tool use regardless of hand used. Praxis with either hand commonly activated the superior parietal lobule, supplementary motor area, premotor area of the left hemisphere, and cerebellar vermis. However, minimal activation occurred in the inferior parietal lobule, which has been known to be a critical area for praxis generation. Compared with left-hand praxis, right-hand praxis exhibited additional activation in the left putamen and posterior part of the left inferior temporal region. Our findings concur with neuropsychological observations that the left hemisphere in right-handers mediates programming and executing skilled movements and that, within the left hemisphere, praxis is predominantly subserved by the parietal lobe, supplementary motor area, and premotor area. However, unlike previous lesion studies, the results of our fMRI study suggested that the superior parietal lobule more likely than the inferior parietal lobule play an important role in gesture production.

Adult↗

An fMRI study of personality influences on brain reactivity to emotional stimuli.

Functional imaging studies have examined which brain regions respond to emotional stimuli, but they have not determined how stable personality traits moderate such brain activation. Two personality traits, extraversion and neuroticism, are strongly associated with emotional experience and may thus moderate brain reactivity to emotional stimuli. The present study used functional magnetic resonance imaging to directly test whether individual differences in brain reactivity to emotional stimuli are correlated with extraversion and neuroticism in healthy women. Extraversion was correlated with brain reactivity to positive stimuli in localized brain regions, and neuroticism was correlated with brain reactivity to negative stimuli in localized brain regions. This study provides direct evidence that personality is associated with brain reactivity to emotional stimuli and identifies both common and distinct brain regions where such modulation takes place.

Adult↗

Late postictal residual perfusion abnormality in epileptogenic zone found on 6-hour postictal SPECT.

BACKGROUND: Temporal evolution of regional hyperperfusion in the late postictal stage in epilepsy has not been clearly defined. OBJECTIVE: To establish the late temporal evolution of the perfusion in epileptogenic zones using 6-hour postictal SPECT. METHODS: Ictal 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT was performed in 10 patients with intractable epilepsy (4 temporal lobe epilepsy, 6 neocortical epilepsy) followed by delayed acquisition and another 6-hour postictal SPECT after reinjection of 99mTc-HMPAO. The delayed acquired SPECT was subtracted from the reinjection SPECT to yield the 6-hour postictal SPECT. Interictal SPECT was acquired on another day. Late postictal perfusion was examined visually, and asymmetric indexes were compared with each other on ictal, 6-hour postictal, and interictal SPECT. RESULTS: Ictal SPECT images of delayed acquisition were visually and quantitatively similar to those of early acquisition. In 7 of 10 patients, 6-hour postictal SPECT showed hyperperfusion. In one patient, the 6-hour postictal SPECT image showed less perfusion than the interictal SPECT image in the epileptogenic zone. CONCLUSIONS: Late postictal hyperperfusion was found in more than half of the patients. Postictal perfusion abnormalities did not come back to the interictal phase 6 hours after ictus and these were identified on ictal/postictal 99mTc- HMPAO SPECT.

Adolescent↗

A pilot study of systemic corticosteroid administration in conjunction with intrapleural adenoviral vector administration in patients with malignant pleural mesothelioma.

One of the primary limitations of adenoviral (Ad) -mediated gene therapy is the generation of anti-Ad inflammatory responses that can induce clinical toxicity and impair gene transfer efficacy. The effects of immunosuppression on these inflammatory responses, transgene expression, and toxicity have not yet been systematically examined in humans undergoing Ad-based gene therapy trials. We therefore conducted a pilot study investigating the use of systemic corticosteroids to mitigate antivector immune responses. In a previous phase I clinical trial, we demonstrated that Ad-mediated intrapleural delivery of the herpes simplex virus thymidine kinase gene (HSVtk) to patients with mesothelioma resulted in significant, but relatively superficial, HSVtk gene transfer and marked anti-Ad humoral and cellular immune responses. When a similar group of patients was treated with Ad.HSVtk and a brief course of corticosteroids, decreased clinical inflammatory responses were seen, but there was no demonstrable inhibition of anti -Ad antibody production or Ad-induced peripheral blood mononuclear cell activation. Corticosteroid administration also had no apparent effect on the presence of intratumoral gene transfer. Although limited by the small numbers of patients studied, our data suggest that systemic administration of steroids in the context of Ad-based gene delivery may limit acute clinical toxicity, but may not inhibit cellular and humoral responses to Ad vectors.

Adenoviridae↗

Clinical and laboratory evidence for a trilineage haematopoietic defect in patients with refractory Diamond-Blackfan anaemia.

Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral blood counts and bone marrow (BM) aspirates and biopsies. In 21/28 (75%) patients, moderate to severe generalized BM hypoplasia developed, with overall cellularities ranging from 0% to 30%. Marrow hypoplasia correlated with the development of neutropenia (9/21; 43%) and/or thrombocytopenia (6/21; 29%) in many patients. No patient had either cytogenetic abnormalities or progressed to acute leukaemia, although one 13-year-old developed marked marrow fibrosis and trilineage dysplasia. We used the in vitro long-term culture-initiating cell (LTC-IC) assay to quantify multilineage, primitive haematopoietic progenitors in a representative subset of these patients. LTC-IC assays showed equivalent frequencies of cobblestone area-forming cells (CAFCs) with a mean of 5.42/10(5) cells +/- 1.9 SD and 6.13/10(5) cells +/- 2.6 SD in nine patients and six normal controls respectively. The average clonogenic cell output per LTC-IC, however, was significantly lower in DBA patients (mean 2.16 +/- 1.2 SD vs. 7. 36 +/- 2.7 SD in normal controls, P = 0.0008). Our results suggest that the underlying defect in patients with severe refractory DBA may not be limited to the erythroid lineage, as was evidenced by the development of pancytopenia, bone marrow hypoplasia and reduced clonogenic cell output in LTC-IC assays.

Adolescent↗

Bioavailability of itraconazole in rats and rabbits after administration of tablets containing solid dispersion particles.

A tablet dosage form containing solid dispersions of itraconazole (Asd tablets) was prepared by using the spray-drying and wet granulation methods. The dissolution rate of itraconazole from Asd tablets was fast, with more than 90% released within 10 min, compared to less than 20% for a marketed product, Sporanox capsules. The oral absorption of itraconazole from Asd tablets was determined in rats and rabbits and was compared with that for Sporanox capsules. In the rat, there was no difference between the Asd tablets and Sporanox capsules in the mean area under the curve (AUC) (3089.5 +/- 4332.8 ng.hr/ml and 3653.9 +/- 2348.9 ng.hr/ml, respectively) and Cmax (295.0 +/- 344.5 and 390.5 +/- 169.4 ng/ml, respectively). Also, in the rabbit, no difference was found between the two products in the mean AUC (AUMC; 19357.9 +/- 5117.5 ng.hr/ml and 23382.2 +/- 6236.5 ng.hr/ml, respectively) and Cmax (766.4 +/- 276.5 and 1127.5 +/- 577.9 ng/ml, respectively). Despite the rapid in vitro release characteristics of itraconazole from the Asd tablets, the in vivo absorption of itraconazole was comparable to that of Sporanox capsules, with no difference in Tmax in both animal species. Serum levels of the major active metabolite hydroxyitraconazole were also measured. Itraconazole was rapidly converted to hydroxyitraconazole in both rats and rabbits, but there were species-specific differences in their pharmacokinetics. It is concluded that, in addition to drug solubility and dissolution characteristics, other formulation factors such as the physical state of the drug and the granulation process, may also need to be considered in the prediction of the in vivo absorption of itraconazole based on in vitro data.

Animals↗

Absorption, first-pass metabolism, and disposition of itraconazole in rats.

This study examined the pharmacokinetic disposition, oral absorption and hepatic extraction of itraconazole and its active metabolite, hydroxyitraconazole, in rats. After i.v. injection, serum itraconazole concentrations decreased biexponentially, with an average terminal elimination half-life, volume of distribution and systemic clearance of 4.9 h, 6.0 l/kg and 14.2 ml/min/kg, respectively. When given orally, its absorption was low, with a mean absolute bioavailability of 16.6%. The metabolite to parent drug area under the curve (AUC) ratio was higher after oral administration compared with i.v. injection (mean ratio, 2.7 vs. 0.9). The hepatic drug extraction ratio determined after femoral and portal vein administration averaged 18.5%. When hydroxyitraconazole was injected i.v., the elimination half-life, volume of distribution and systemic clearance of itraconazole averaged 10.0 h, 2.4 l/kg and 3.4 ml/min/kg, respectively. The fraction of the systemically available itraconazole that was metabolized to hydroxyitraconazole was 21.0% and 76.0% after i.v. and oral administration, respectively. In summary, this study is the first reporting the hepatic extraction of itraconazole and the i.v. disposition characteristics of hydroxyitraconazole in rats. Itraconazole is a drug with a low hepatic extraction ratio and its systemic clearance appears to be largely accounted for by hepatic metabolism.

Administration, Oral↗

Single-shot echo-planar imaging of multiple sclerosis: effects of varying echo time.

Our aim was to determine the relative merits of short and long echo times (TE) with single-shot echo-planar imaging for imaging cerebral lesions such as multiple sclerosis. We examined seven patients with clinically definite multiple sclerosis were imaged at 1.5 T. Patients were scanned with spinecho, single-shot echo-planar imaging, using TEs of 45, 75, 105, and 135 ms. Region of interest (ROI) measurements were performed on 36 lesions at or above the level of the corona radiata. The mean image contrast (IC) was highest (231.1) for a TE of 45 ms, followed by 75 ms (218.9), 105 ms (217.9), and 135 ms (191.6). When mean contrast-to-noise ratios (C/N) were compared, the value was again highest (29.7) for TE 45 ms, followed by 75 ms (28.9), 105 ms (28.5), and 135 ms (26.3). In a lesion-by-lesion comparison, TE 45 ms had the highest IC and C/N in the largest number of cases (50 % and 47.2 %, respectively). IC and C/N for TE 45 ms were superior to those of 75 ms in 64% and 58%, respectively. These results support the use of relatively short TEs for single-shot echo-planar imaging in the setting of cerebral lesions such as multiple sclerosis.

Cerebral Cortex↗

Advanced glycation end products induce apoptosis and procoagulant activity in cultured human umbilical vein endothelial cells.

Hyperglycemia and the late products of non-enzymatic glycosylation, called advanced glycation end products (AGEs), play an important role in the development of microvascular complications in diabetes mellitus. Previous studies have reported that a high glucose environment triggered apoptotic changes in human umbilical vein endothelial cells (HUVECs). Therefore, we investigated whether AGEs contribute to the development of apoptosis and prothrombotic activity in HUVECs. After incubation of HUVECs with 0.2, 2.2, 22, 220 and 2200 nM of AGE-bovine serum albumin (BSA) from 6 to 48 h, we assayed the degree of apoptosis and procoagulant activity (PCA). There were no significant differences between HUVECs cultured for 48 h with 0.2, 2.2 or 22 nM of AGE-BSA and in controls in the proportion of apoptotic cells (3.5 +/- 0.8%, 3.9 +/- 1.5% and 5.2 +/- 1.1% vs. 2.5 +/- 0.6%). However, the proportion of apoptotic cells increased significantly to 36.7 +/- 9.8% in 220 nM of AGE-BSA, and 72.3 +/- 10.2% in 2200 nM of AGE-BSA (P < 0.001). PCA levels were 142 +/- 10 s after 6 h of exposure to 22 nM (P < 0.01), 131 +/- 5 s after 6 h of exposure to 220 nM (P < 0.001), and 106 +/- 4 s after 6 h of exposure to 2200 nM of AGE-BSA (P < 0.001). These values show that PCA was shortened significantly from the basal value of 161 +/- 6 s, and remained below the basal level until the end of the study. The amount of tissue factor was also significantly increased in 22 and 220 nM of AGE-BSA compared to the controls. In conclusion, this study showed that AGEs could induce apoptosis and increase procoagulant activity in cultured HUVECs. We suggest that AGEs can contribute to the development of microvascular complications through cell death of HUVECs and functional changes of the blood vessels.

Apoptosis↗