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Biomedical subjects

W Qian

Publications and source records attributed to W Qian.

At least 73 records · Page 4Linked to original sources

Variation in in-patient stroke management in ten centres in different countries: the INCLEN multicentre stroke collaboration.

BACKGROUND AND PURPOSE: Large within-country variations have been described in stroke management and there have been a few studies of between-country variation (in the USA and the UK). We designed a study to examine stroke management across a wide range of countries representing different stages of economic development. Large variations would suggest the need to explore methods of increasing the uptake of evidence-based stroke practice. METHODS: Members of the International Clinical Epidemiology Network (INCLEN) from 14 centres in ten countries agreed to review the records of the last 50 patients admitted to hospital with a clinical diagnosis of stroke. Information on demographic variables, the clinical diagnosis of stroke type, investigations performed and treatments given and the discharge destination of the patient were recorded and sent to the coordinating centre in Australia for analysis. RESULTS: There were statistically significant between-centre differences in the proportions of patients cared for by a neurologist, staying in hospital for at least ten days and having CT or MRI scans. Significant between-centre differences were also seen for treatment, for example, the use of aspirin in non-haemorrhagic stroke varied from 11 to 79%. The variation (for all interventions studied) was no longer statistically significant when examined within strata according to availability of facilities. CONCLUSIONS: The large variation between centres in the management of stroke is largely 'explained' by the availability of resources, even for interventions that do not depend on resource availability. It will be important to develop management guidelines that reflect evidence-based practice of relevance across a range of economic settings.

Age Factors↗

Nitric oxide accumulation in the nonventilated nasal cavity.

BACKGROUND: Nasal nitric oxide is present in high concentrations in the upper airway relative to the lower respiratory tract. OBJECTIVE: To explore the rate of nitric oxide accumulation in the nonventilated nasal cavity. METHODS: In 9 healthy subjects previously trained to close the soft palate, steady-state plateau nitric oxide levels were recorded while air was aspirated through the nasal airway in series at a constant flow rate. Nitric oxide was then allowed to accumulate in the nasal cavity by occluding both nares and keeping the velum closed. After varying occlusion times, peak nitric oxide levels and a second plateau were ascertained. RESULTS: While the subjects aspirated air at a constant flow, there was a slow rise to a first nitric oxide plateau. On opening to the analyzer after the accumulation period, the peak nitric oxide level was several times higher than the initial plateau (range, 2810-19008 ppb) and then slowly returned to previous plateau levels. There was no significant difference between initial and second plateau nitric oxide levels for any period. The accumulated nitric oxide peak increased in direct proportion to the accumulation time (P<.001). CONCLUSIONS: Nitric oxide concentrations accumulate in the nonventilated nasal cavity in proportion to the time of nonventilation. Peak nasal nitric oxide values after accumulation are similar to published sinus nitric oxide measurements obtained by direct puncture. These results suggest an important alternative source of nitric oxide in humans.

Adult↗

Towards Sixfold Functionalization of Buckminsterfullerene (C(60)) at Fully Addressable Octahedral Sites.

Selective C(60)-functionalizations that provide access to unusual multifunctional molecules are of interest in the construction of highly organized three-dimensional assemblies. The temporary "masking" of three of the most reactive sites on C(60) by a bisdiene tether has allowed the facile and high-yielding formation of the fully differentiated trisadduct 1 and the interesting hexaadduct 2.

Journal Article↗

Digital mammography: comparison of adaptive and nonadaptive CAD methods for mass detection.

RATIONALE AND OBJECTIVES: The authors compared the performance of adaptive and nonadaptive computer-aided diagnostic (CAD) methods for breast mass detection with digital mammography. MATERIALS AND METHODS: Both adaptive and nonadaptive modular CAD methods employed recent advances in multiresolution and mutiorientation wavelet transforms for improved feature extraction. The nonadaptive method uses fixed parameters for the image preprocessing modules. The adaptive method, a new class of algorithms, adapts to image content by selecting parameters for the image preprocessing modules within a parameter range. Comparison of the two methods was performed for each individual CAD module with a region-of-interest (ROI) database containing all mass types and normal tissue. RESULTS: Receiver operating characteristic (ROC) analysis clearly demonstrated an improvement in performance for the three adaptive modules and a significant overall difference between the two methods. The average ROC area index (Az) values were 0.86 and 0.95 for the nonadaptive and adaptive methods, respectively. The corresponding P value is .0145. For a previously reported database of full mammographic images containing 50 abnormal cases with all mass types and 50 normal images, the adaptive CAD method had a sensitivity of 96% (1.71 false-positive results per image) compared with 89% (1.91 false-positive results per image) for the nonadaptive CAD method. CONCLUSION: The adaptive CAD method demonstrated better performance. A study is in progress to determine the generalizability of the adaptive CAD method by applying it to larger retrospective image databases with different film digitizers.

Algorithms↗

Methanol-induced unfolding and refolding of cytochrome b5 and its P40V mutant monitored by UV-visible, CD, and fluorescence spectra.

In order to illustrate the structural importance of proline-40 of cytochrome b5 (Cyt b5), the P40V mutant gene was constructed. Unfolding and refolding of Cyt b5 induced by methanol was investigated by means of the UV-visible spectrum, circular dichroism, and the fluorescence spectrum. Methanol denaturation of Cyt b5 is a cooperative process, that is, the heme group dissociates from the heme pocket accompanied by unfolding of the polypeptide chain both in the secondary and tertiary structures. Substitution of proline by valine reduces the stability of the mutant under methanol denaturation. The unfolding process is almost reversible by dilution. During refolding, the denatured polypeptide must be folded to a more ordered structure prior to the heme capture. Pro40 plays an important role in modulating the protein's stability. The role of tyrosine in the unfolding and refolding of Cyt b5 is evaluated for the first time. A mechanism of methanol denaturation is also proposed.

Animals↗

Aerodynamic influences on nasal nitric oxide output measurements.

Nitric oxide (NO) concentration in aspirated nasal air is flow-dependent. Nasal NO outputs calculated from steady-state plateaux at flows < 1 l/min are substantially smaller than those at flows > 2 l/min. This study aimed to determine the differences in NO output as calculated from the NO concentration plateaux in aspirated nasal air, resulting from different aspiration flows. Nasal NO was determined by chemiluminescent analysis of air obtained from the nasal passages in series during velopharyngeal closure in 8 healthy adults (flows: 0.2-3.7 l/min) and 5 with symptomatic allergic rhinitis (flows: 0.2-3.7 l/min). Mean NO output in the healthy subjects was stable at approximately 315 nl/l/min at flows of 0.2-0.7 l/min, and increased to a second steady output level of approximately 400 nl/l/min (+28%, p < 0.0001) at more physiological flow rates of 2.7 l/min and higher. The symptomatic subjects had substantially higher NO output at all flows (p < 0.001) (709.3 nl/min at 3.7 l/min) than the non-allergic subjects. The flow dependency of the nasal NO output may be explained by failure at low flows for the air stream to penetrate the peripheral parts of the complex nasal passages, and by the presence of a laminar flow regime in which a marginal lamina would tend to insulate the main stream from the mucosa. Thus, previously reported NO outputs obtained at low flows may underestimate nasal NO output compared to output at higher and more physiological transnasal airflow rates, thus affecting interpretation of results.

Adult↗

Long-term weight maintenance after an intensive weight-loss program.

OBJECTIVE: This prospective study assessed long-term weight maintenance of patients completing an intensive very-low-calorie diet (VLCD) weight-loss program. SUBJECTS: Individuals who had completed the 12-week core education program and lost > or = 10 kg were recruited. RESULTS: Of 154 eligible subjects, follow-up weights were obtained at > or = 2 years in 112 subjects (72.7%, 72 women, 40 men). Subjects had an average initial body mass index of 37.3 kg/m2 and an average weight loss of 29.7 kg in five months. Six hundred and forty-five follow-up weights (median, five per subject) were obtained over two to seven years of follow-up from clinic visits (70%) and self-report by telephone or mail (30%). Subjects regained an average of 2.5% per month of their lost weight during the first two to three years of follow-up; however, their weight stabilized over the next four years. Subjects regained an average of 73.4% of their weight loss during the first three years. The average weight loss maintained for 112 subjects was 22.8% of initial weight loss after an average of 5.3 years of follow-up. When successful weight maintenance was defined as maintaining a weight loss of 5% or 10% of initial (pre-treatment) body weight, 40% were maintaining a 5% weight loss at five years and 25% were maintaining a weight loss of 10% at 7 years. Multiple regression analyses suggested that age had a significant (p=0.004) and positive effect on weight maintenance. CONCLUSIONS: This study suggests that weight maintenance after an intensive VLCD program is improving but still needs intensive efforts to enable most individuals to maintain a substantial percentage of their weight loss long-term.

Adult↗

Cytotoxic metabolite of acetaminophen, N-acetyl-p-benzoquinone imine, produces cataract in DBA2 mice.

Acetaminophen, or N-acetyl-p-aminophenol (APAP), is metabolized to N-acetyl-p-benzoquinone imine (NAPQI) by cytochrome P450 enzymes in the liver. The biotransformation of APAP is enhanced in P450-inducible C57BL6 (B6) mice but not in non-inducible DBA2 (D2) mice. Our previous studies showed that high doses of APAP administered to B6 mice pretreated with beta-naphthoflavone (BNF), a P450 inducer, produced ocular tissue damage but not in D2 mice similarly treated. We then proposed that the ocular toxicity of APAP is due to accumulation of its metabolite, NAPQI. In the present work, we tested this hypothesis by injecting NAPQI (50 microg in 2 microl propyleneglycol/eye) intracamerally into B6 and D2 mice. NAPQI produced cataract within a few hours (mean = 4 hr) both in B6 and D2 mice. Lower concentrations of NAPQI did not produce lens opacification. Injection of the solvent propyleneglycol only did not cause cataract. Thus, when NAPQI was injected, P450 inducibility was not essential for cataract formation. In addition to vacuole formation in the lens epithelial cells, alterations were observed in the corneal endothelium and ciliary epithelium. The retinal cell layers remained intact. Extensive mitochondrial damage and changes in chromatin structure in the nucleus were evident in the affected lens epithelial cells. The present result dissociates APAP ocular toxicity from its metabolic potentiation by P450 enzymes and will allow us to investigate the mechanism of cataractogenesis in in vitro lens culture systems.

Acetaminophen↗

Aspiration flow optimized for nasal nitric oxide measurement.

The aim of the present study was to evaluate some of the factors which may influence the reliability of nasal NO measurements, and to optimize methods suitable for children and adults. Nasal nitric oxide (NO) output was determined by chemiluminescent analysis of aspirated samples in 16 adults and 6 children. With the velopharyngeal aperture closed, stable NO levels were obtained at flows ranging form 0.9 to 6.2 L/min. NO output averaged 401.0 +/- 145.4 nL/min./M2 in 6 children, 338.2 +/- 92.3 in 7 adult females and 268.6 +/- 70.2 in 9 adult males. Nasal NO output was independent of flow provided a stable plateau of NO value was reached. In this study, the optimal range of flows was 3.2-5.2 L/min. in adults and 2.2-3.2 L/min. in children. This enables selection of the most favorable flow to be chosen for individual subjects and situations.

Adult↗

Is conversion of solid into more anoxic ascites tumors associated with p53 inactivation?

Most solid tumors are unable to grow in the ascites form, unless selected by prolonged serial transfer of peritoneal fluid (Klein, 1955). Established ascites tumor cells grow under highly crowded, virtually anoxic conditions (Warburg and Hiepler, 1953). Hypoxia was recently identified as a powerful inducer of p53 dependent apoptosis (Graeber et al., 1996). We wished to examine whether the conversion of relatively well-vascularized solid mouse tumors into freely growing ascitic cell variants favors cell with mutated or deleted p53. We have sequenced exons 4-9 of p53 cDNA from two serially transplanted methylcholanthrene induced sarcomas (MCIM and MSWBS) that were available in the original solid and the gradually converted ascites form. We have also examined five additional solid tumors, four carcinomas and one sarcoma and six additional ascites tumors, five carcinomas and one sarcoma. Sequence analysis showed that all solid tumors carried exclusively wild type p53. Among the eight ascites tumors, five carried mutant p53 and three had only the wild type gene. In one of the two isogenic pairs, the original solid tumor line had only wild type, whereas the derived ascites line had only mutant p53. In the second pair, the solid tumor was wild type whereas the ascitic variant was heterozygous. The naturally occurring alternatively spliced p53 (p53as) mRNA was detected in all solid tumors, but not in five of the eight ascites tumors. Our findings indicate that conversion of solid into ascites tumors favors the selection of cell variants with mutated p53 and of cells that lack the alternatively spliced form of p53.

Animals↗

The influence of mutation at Glu44 and Glu56 of cytochrome b5 on the protein's stabilization and interaction between cytochrome c and cytochrome b5.

To characterize the roles played by Glu44 and Glu56 of cytochrome b5 in the formation of the electrostatic complex between cytochrome c and cytochrome b5, the Glu44, Glu56, or both sites were changed to alanine by site-directed mutagenesis. The influence of these two residues on the protein stability was probed by investigating the kinetic behaviors of protein denaturation in urea or upon heating and the heme-transfer reactions between apo-myoglobin and the variants of cytochrome b5. It has been found that when the Glu44 and/or Glu56 are mutated to alanine, the protein stability increases slightly due to the fact that the hydrophilic residue is changed to a hydrophobic one, resulting in the two pairs of helices surrounding the heme taking a more compact conformation. The difference in voltammetric behavior of cytochrome c, cytochrome b5, and its three mutants, Cyt b5 E44A, E56A, and E44/56A, alone and in 1:1 protein complexes demonstrates that both Glu44 and Glu56 of cytochrome b5 take part in the electrostatic interaction with cytochrome c. The entropy changes, DeltaS degreesrc and enthalpy changes, DeltaH degrees, derived from the temperature dependence of the formal reduction potentials of each protein in different protein systems suggest that, because of the mutual interaction with cytochrome c, cytochrome b5 mutants, especially the E44A-containing mutants, in the protein complexes suffer greater conformational changes upon reduction than that of the wild type. The variation of these thermodynamic parameters indicates that the strength of mutual interactions between cytochrome c and cytochrome b5 or its mutants has the following order: Cyt c/Cyt b5 > Cyt c/Cyt b5 E56A > Cyt c/Cyt b5 E44A > Cyt c/Cyt b5 E44/56A.

Animals↗

Cellular and subcellular heterogeneity of glutathione metabolism and transport in rat kidney cells.

Selective permeabilization of plasma membranes with digitonin produced separation of cytosolic and mitochondrial compartments of proximal tubular (PT) and distal tubular (DT) cells from a rat kidney. Subcellular distributions of several intracellular glutathione (GSH)-dependent enzymes were similar in the two cell types but specific activities were significantly higher in PT cells, indicating that DT cells, particularly in their mitochondrial fraction, have a diminished capacity to detoxify reactive oxygen species. To enable isolation of suspensions of mitochondria, renal cells were treated with digitonin followed by the bacterial protease nagarse and were filtered through polycarbonate membranes. Activity distributions of enzymatic markers for subcellular fractions were quantitated and uptake of GSH was studied in suspensions of PT and DT cell mitochondria. While PT cell mitochondria catalyzed rapid uptake of GSH that was inhibited by malate, indicating involvement of dicarboxylate carriers, DT cell mitochondria exhibited limited capacity for GSH uptake that was not inhibited by substrates for the two dicarboxylate carriers. This report provides the first description of methodology for the preparation of mitochondria from renal cells derived from specific nephron cell types and shows that mitochondria from DT cells have a significantly lower capacity to use GSH for detoxification and regulation of redox status.

Animals↗

Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences.

Perchloroethylene (Per)-induced nephrotoxicity and nephrocarcinogenicity have been associated with metabolism by the glutathione (GSH) conjugation pathway to form S-(1,2,2-trichlorovinyl)glutathione (TCVG). Formation of TCVG was determined in incubations of Per and GSH with isolated renal cortical cells and hepatocytes from male and female Fischer 344 rats and with renal and hepatic cytosol and microsomes from male and female Fischer 344 rats and B6C3F1 mice. The goal was to assess the role of metabolism in the sex and species dependence of susceptibility to Per-induced toxicity. A key finding was that GSH conjugation of Per occurs in kidney as well as in liver. Although amounts of TCVG formation in isolated kidney cells and hepatocytes from male and female rats were generally similar, TCVG formation in subcellular fractions showed marked sex, species, and tissue dependence. This may be due to the presence of multiple pathways for metabolism in intact cells, whereas only the GSH conjugation pathway is active in the subcellular fractions under the present assay conditions. TCVG formation in kidney and liver subcellular fractions from both male rats and mice were invariably higher than corresponding values in female rats and mice. Amounts of TCVG formation in rat liver subcellular fractions were approximately 10-fold higher than in corresponding fractions from rat kidney. Although rats are more susceptible to Per-induced renal tumors than mice, amounts of TCVG formation were 7- to 10-fold higher in mouse kidney subcellular fractions and 2- to 5-fold higher in mouse liver subcellular fractions of both sexes compared to corresponding fractions from the rat. Hence, although the higher amounts of TCVG formation in liver and kidney from male rats correspond to their higher susceptibility to Per-induced renal tumors compared with female rats, the markedly higher amounts of TCVG formation in mice compared with rats suggest that other enzymatic or transport steps in the handling of Per in mice contribute to their relatively low susceptibility to Per-induced renal tumors

Animals↗

The role of ras gene mutation in gastric cancer and precancerous lesions.

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia, atypical hyperplasia, early-stage cancer and advanced cancer was 16.7%, 31.2%, 50.0%, and 32.2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of H-ras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G-->T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P < 0.05, P < 0.01, P < 0.01, respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.

Gastric Mucosa↗

Digital mammography: hybrid four-channel wavelet transform for microcalcification segmentation.

RATIONALE AND OBJECTIVES: The authors evaluated an algorithm for the automatic segmentation of microcalcification clusters (MCCs) at digital mammography. Two- and four-channel wavelet transforms were evaluated to determine whether sensitivity in the detection of MCCs can be improved and if the selective reconstruction of the higher-order M2 subimages allows better preservation of the segmented MCCs, which is required for their classification. MATERIALS AND METHODS: The hybrid method involved the use of a nonlinear filter for image noise suppression coupled with wavelet transforms for image decomposition and an adaptive method for selective subimage reconstruction as a basis for segmentation of MCCs. The two- and four-channel wavelet transforms were implemented with different filter bank structures (i.e., polyphase quadrature mirror filters [QMFs], tree structure, and lattice structure) to determine if their computational efficiency can be improved while retaining properties such as near-perfect reconstruction. The hybrid wavelet transforms were applied to a common image database of biopsy-proved MCCs (100 images, 105-micron resolution, 12 bits deep; 52 cases with at least one MCC of varying subtlety [46 malignant and six benign cases] and eight normal cases). RESULTS: The two- and four-channel wavelet transforms yielded sensitivities of 93% and 94% and false-positive (PP) detection rates of 1.58 and 1.35 MCCs per image, respectively. The lattice structure provided greater than fivefold improvement in computational speed compared to the polyphase QMF structure, particularly for the higher order of channels (M = 4). CONCLUSION: The four-channel wavelet transform provided better sensitivity and FP detection rates and greater image detail preservation for the segmented MCCs.

Algorithms↗

Fragmentary window filtering for multiscale lung nodule detection: preliminary study.

RATIONALE AND OBJECTIVES: The authors evaluated computer-assisted diagnostic (CAD) methods used to detect suspicious areas on lung radiographs. MATERIALS AND METHODS: The authors designed a fragmentary window filtering (FWF) algorithm for detecting lung nodule patterns, which generally appear as circular areas of high opacity on the chest radiograph. The FWF algorithm helps differentiate circular patterns from overlapping radiographic background. A multiscale analysis was performed to locate multiscale nodules. Receiver operating characteristic analysis was performed by using a lung nodule that was extracted from a chest radiograph. The nodule underwent scalings and subsequent superimposition onto 140 normal regions of interest from six chest radiographs. RESULTS: The FWF method was superior to the matched filtering method in the detection of suspicious areas. CONCLUSION: The proposed FWF-based method should provide improved detection of lung nodules on chest radiographs.

Algorithms↗

Effect of histidine on myocardial mitochondria and platelet aggregation during thrombotic cerebral ischemia in rats.

AIM: To study the effect of histidine on cerebral thrombosis and possible mechanism. METHODS: Cerebral-cardiac stroke was produced by photochemically induced thrombotic cerebral ischemia in rats. RESULTS: Platelet aggregation in whole blood increased markedly, peak heights at 4 and 24 h were (5.1 +/- 0.5) omega and (4.3 +/- 0.5) omega, respectively. Heart mitochondria volume (V), volume density (Vv), surface density (Nm), and surface density of outer membrane (Sv1) increased (8.2 +/- 5.5, 0.59 +/- 0.16, 0.11 +/- 0.03, and 0.22 +/- 0.05, respectively, P < 0.01), but numerical density (Nv), specific surface of inner membrane (delta 2) and of the cristae (delta 3) decreased (0.07 +/- 0.02, 2.8 +/- 0.8, and 2.4 +/- 0.7, respectively, P < 0.01) after cerebral thrombosis. The myocardial histopathologic characteristics were different from those of ischemic necrosis and myocardial damage caused by ischemic reperfusion. In rat treated with histidine after photochemical reaction, platelet aggregation decreased markedly [(2.93 +/- 1.08) omega, P < 0.01], reversible change often went with parameters related to the inner mitochondrial membrane but not the outer mitochondrial membrane. CONCLUSION: Histidine depressed platelet aggregation and reduced myocardial mitochondrial damage resulted from cerebral ischemia.

Animals↗

[Expression of proliferating cell nuclear antigen in hemangioma and vascular malformations].

OBJECTIVE: This study was to compare the proliferative activity of endothelial cells of various types of hemangiomas and vascular malformations in different phases. METHODS: Forty-one specimens of hemangiomas or vascular malformations from biopsy or operative resection were stained with immunohistochemical method for proliferating cell nuclear antigen (PCNA). The proliferative activity of endothelial cells was expressed by labeling index (LI). RESULTS: PCNA was positive in all of proliferating strawberry, composite hemangiomas and some of cavernous hemangiomas in children. PCNA was negative in all of adult involuted hemangiomas and some of cavernous hemangiomas in children. There were no statistically significant differences in labeling indices of PCNA between various types of proliferating hemangiomas in children while there were statistically significant differences between child proliferating hemangiomas and involuted hemangiomas in children or all of adult hemangiomas. CONCLUSION: The results may be helpful to answer some bewildering questions about hemangiomas and provide a basis for new classification.

Adult↗