Biomedical subjects
Publications and source records attributed to Qing Dai.
Doping the molecular plastic crystal of succinonitrile with solid N-methyl-N-butylpyrrolidinium iodide salt and iodine has produced a highly conductive solid iodide/triiodide conductor. Furthermore, it was employed for a highly efficient, all-solid-state dye-sensitized solar cell.
[reaction: see text] Metal ion rescue experiments provide a powerful approach to establish the presence and role of divalent metal ions in the biological function of RNA. The utility of this approach depends on the availability of suitable nucleoside analogues. To expand the range of this experimental strategy, we describe the first synthesis of 2',3'-dideoxy-2'-amino-3'-thiouridine (12) in 19.5% overall yield starting from 2,2'-anhydrouridine (1).
Efficient new syntheses of the o-quinone derivatives of benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding o-catechols, trans-dihydrodiols, and the corresponding anti- and syn-diol epoxides.
A convenient new synthesis of the ubiquitous environmental carcinogen benzo[a]pyrene (BaP) is described. In the key step, the method entails Suzuki coupling of naphthalene 2-boronic acid with 2-bromobenzene-1,3-dialdehyde and requires only three steps. It is considerably shorter and simpler than the older methods and provides BaP in higher overall yield.
The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 +/- 19 degrees. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 +/- 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 +/- 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.
OBJECTIVE: To develop a noninvasive method and device to determine intravariceal pressure and variceal wall tension by measuring the variables of the Laplace equation and test this device in a model of esophageal varices. METHODS: Two variceal pressure measurement devices were constructed. The first device consists of an Olympus 20 MHz ultrasound transducer placed next to a latex balloon catheter attached to a pressure transducer. The second device was constructed by placing the same ultrasound transducer inside a latex condom balloon attached to a pressure transducer. These pressure measurement devices were tested blindly in varix models with different intravariceal pressures, by inflating the balloon to flatten the varix models. Each variceal pressure was measured 10 times by two separate investigators blinded to the actual pressures. The mean intravariceal pressures were calculated. The variceal models were made of a latex balloon filled with water and coffeemate. RESULTS: The correlation coefficient between the actual and measured varix pressures for both devices was 0.99. The percent error ranged from 0 to 10%. The correlation coefficient between the investigators making the blinded measurements for both devices was 0.98. CONCLUSION: Two pressure-measuring devices were developed to determine intravariceal pressure in a model varix system. These devices demonstrate a low percent error and a high correlation to the actual variceal pressures with low intra- and interobserver variability. These devices have the potential to measure all the variables of the Laplace equation for wall tension. We plan to test these devices in human subjects.
Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.
[reaction: see text] 2'-C-beta-Fluoromethyluridine (17) represents both a potentially important biological agent and a tool for biochemical analysis. Here we describe the first synthesis of this compound starting from uridine. The key steps include protection of the uracil base with methoxyethoxymethyl (MEM) chloride, conversion to the corresponding 2'-C-alpha-epoxide, and regioselective opening of the oxirane ring with potassium fluoride/hydrogen fluoride. Subsequent acetylation of the 3'- and 5'-hydroxyl groups enables MEM removal using B-bromocatecholborane. Deacetylation generates the parent nucleoside, 2'-C-beta-flurormethyluridine.
BACKGROUND: Conventional 3-dimensional endoluminal US was modified to evaluate peristaltic contractions in the esophagus. METHODS: Two-dimensional US images and simultaneous intraluminal pressures were acquired during peristaltic contractions by locating the transducer at fixed positions in the esophagus in 6 normal volunteers during swallowing. Three-dimensional images were reconstructed by using a computer-based 3-dimensional algorithm with time as the x axis. RESULTS: The peristaltic contraction sequence was viewed as a 3-dimensional US image. The geometric configuration of the esophagus, the muscle thickness, and corresponding pressures were evaluated. The 3-dimensional images demonstrate 4 phases of the peristaltic contraction sequence. CONCLUSIONS: Three-dimensional time-resolved reconstruction of endoluminal US images of the esophagus and simultaneous recording of manometric data allow visualization of geometric changes and correlation with pressure changes during peristaltic contraction. Four phases of the peristaltic contraction sequence are demonstrated clearly on the 3-dimensional space-time images.
The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.
BACKGROUND: Esophageal varices are a frequent source of bleeding in patients with cirrhosis. Elevated intravariceal pressure is associated with variceal bleeding. There is no simple, easy-to-use device for noninvasive measurement of intravariceal pressure. The purposes of this study were to develop a noninvasive method for measuring intravariceal pressure, and to develop a model of esophageal varices that can be used to test this pressure measurement device. METHODS: A variceal pressure measurement device was constructed by placing a 20 MHz US transducer in a latex balloon catheter sheath and attaching the catheter to a pressure transducer. The pressure measurement device was passed though the accessory channel of a large-channel endoscope and tested in blinded fashion by using tip deflection to compress each of 4 variceal models with the device. The pressure within each model was measured 10 times by 2 separate investigators blinded to the actual pressures. The mean (SD) pressure was calculated for each model. The variceal models were made of nitrocellulose dialysis tubing filled with water. Each "varix" had the same diameter but a different intraluminal pressure (5.5, 10, 15, 21.5 mm Hg). OBSERVATIONS: The correlation coefficient between the actual and measured "varix" pressures for the first investigator (L.S.M.) was r = 0.96: 99% CI [0.93, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 9.5, 3.9, 5.1, and 0.7. The correlation coefficient between the actual and measured varix pressures for the second investigator (Q.D.) was r = 0.97: 99% CI [0.94, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 10.3, 3.4, 9.8, and 1.1. The correlation coefficient between the 2 investigators (L.S.M., Q.D.) for the varix model pressures was r = 0.97: 99% CI [0.95, 0.99]. CONCLUSION: The variceal pressure measuring device developed for this study measured intravariceal pressure in a model varix with a low percent error and high correlation to the actual pressures. Intraobserver and interobserver variability was low.
The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) regulates immune responses, inflammation, and programmed cell death (apoptosis). TNF-alpha exerts its biological activities by activating multiple signaling pathways, including IkappaB kinase (IKK), c-Jun N-terminal protein kinase (JNK), and caspases. IKK activation inhibits apoptosis through the transcription factor NF-kappaB, whose target genes include those that encode inhibitors of both caspases and JNK. Despite activation of the antiapoptotic IKK/NF-kappaB pathway, TNF-alpha is able to induce apoptosis in cells sensitive to it, such as human breast carcinoma MCF-7 and mouse fibroblast LM cells. The molecular mechanism underlying TNF-alpha-induced apoptosis is incompletely understood. Here we report that in TNF-alpha-sensitive cells activation of the IKK/NF-kappaB pathway fails to block TNF-alpha-induced apoptosis, although its inactivation still promotes TNF-alpha-induced apoptosis. Interestingly, TNF-alpha-induced apoptosis is suppressed by inhibition of the JNK pathway but promoted by its activation. Furthermore, activation of JNK by TNF-alpha was transient in TNF-alpha-insensitive cells but prolonged in sensitive cells. Conversion of JNK activation from prolonged to transient suppressed TNF-alpha-induced apoptosis. Thus, absence of NF-kappaB-mediated inhibition of JNK activation contributes to TNF-alpha-induced apoptosis.
OBJECTIVE: To study the sonographic features and patterns of cystic renal carcinomas. METHODS: Thirteen cases of cystic renal carcinoma confirmed by operation and pathology were examined by ultrasonography, and the cystic walls, septa and solid mural nodules were studied. RESULTS: Solid mural nodules of some cases and irregular thickening of the cystic walls and septa were characteristic findings for the ultrasonic diagnosis of cystic renal carcinomas. According to their pathologic mechanisms and sonographic features, cystic renal carcinomas were classified into 3 patterns: unilocular cystic mass, multiloculated cystic mass and cystic-solid mass. CONCLUSIONS: Typical cystic renal carcinomas can be well diagnosed, while atypical cases may be misdiagnosed as benign renal cysts by ultrasonography. Color Doppler ultrasonography and needle aspiration guided by ultrasonography are helpful in the diagnosis of these atypical cases.
BACKGROUND: Hepatitis C virus infection is a great issue in China; however, there is very little information on genotyping investigations based on sequence variability in the 5'untranslated (5'UTR) reported. The present study was to define the sequence variability based on the sequence divergences of the 5'UTR of the virus. METHODS: Sequences of 91 isolates from patients with chronic hepatitis C from Yunnan, southwest China, were sequenced and genotypes were defined according to the sequence divergences of the 5'UTR of the virus. RESULTS: Eighty-six isolates were classified into 3 clades (previously termed groups or major types) by the methods proposed by Chan et al in 1992 and phylogenetic analysis based on nucleotide sequence divergences within the 5'UTR. Fifty-six percent of the isolates were classified into clade 3, 35% into clade 1, and 34.9% into clade 2. New genotypes 1f, 2h, 3h and 3i were defined. In addition, 3 novel sequences were discovered, respectively with an 18-nt sequence deletion (corresponding to nucleotide position -173 to -156), a 28-nt sequence insertion, and a 40-nt sequence insertion, between -56 and -55. Of these isolates, 56% possessed a "G" at position -66 in place of the "T" that is present in all previously reported sequences. CONCLUSIONS: These HCV variants, evolved or remained in this area, may be of great significance in diagnosis and treatment of hepatitis C patients.
OBJECTIVE: To define the conditions of hepatitis C virus (HCV) infections, and geographic and demographic distributions of genotypes in China. METHODS: HCV infected patients were selected from individuals with different patterns of liver diseases and high risk populations in different parts of China. Genotypes of HCV in some isolates were further analyzed, based on the data from our laboratory studies and some carefully selected published literatures. RESULTS: The anti-HCV positive rates were 9.7% in patients with acute hepatitis, 13.3% in patients with chronic hepatitis, 18.3% in patients with hepatocellular carcinoma, 33.0% in patients with liver cirrhosis, and 43.2% in patients with posttransfusional hepatitis (average, 16.2% in patients with liver diseases). The anti-HCV positive rates in the high risk populations were 36.4% in leukemic patients, 43.0% in hemodialysis patients, 12.7% in blood donors, 64.1% in drug abusers, 13.1% in prostitutes, and 2.57% in naturally healthy people. At least 4 clades (clades 1, 2, 3 and 6) of HCV were found in China with different geographic and demographic distributions. Genotype 1b was the most widely distributed genotype, and genotype 3 was mainly found in Yunnan Province, Southwest China. CONCLUSION: China has a high incidence of HCV infection. Our results will provide a strategic basis for diagnosis, treatment and possibly prophylaxis of hepatitis C virus diseases.
PURPOSE: The purpose of this prospective study was to evaluate and determine criteria for locating acquired arteriovenous fistulas using color Doppler sonography. METHODS: We performed color Doppler sonography on 12 consecutive patients with acquired arteriovenous fistulas. We evaluated the morphologic and hemodynamic changes in the involved vessels to help locate the fistulas (10 in the extremities, 1 in the neck, and 1 in the abdomen). RESULTS: In all cases, turbulent high-velocity flow spectrum and flow signals were present at the fistula sites, and arterialized waveforms from the draining veins were detected. In the 10 cases of acquired arteriovenous fistulas in the extremities, the resistance indices in the arteries proximal to the fistulas were all less than 1.00 (mean, 0.65), whereas the resistance indices in the arteries distal to the fistulas were all 1.00 or greater (mean, 1.17). In 70% of the cases, the diameter of the artery proximal to the fistula was at least 1.2 mm larger than that distal to the fistula. The fistula site was inferred by the point of maximal venous dilatation in 70% of the cases and by the focal perivascular color artifact in 82% of the cases. The fistula site was identified on gray-scale sonography and color flow imaging in 33% and 75% of the cases, respectively. CONCLUSIONS: Fistula sites can be located effectively and quickly by a combination of major and minor diagnostic criteria. The major diagnostic criteria are (1) junction of low- and high-resistance flow in the supplying artery, (2) a high-velocity arterialized waveform in the draining vein, and (3) a turbulent, high-velocity flow spectrum at the junction of the artery and the vein. The minor diagnostic criteria are (1) direct communication between the involved artery and vein, (2) significant change in the diameter of the supplying artery, (3) a focal point of venous dilatation, and (4) a focal perivascular color artifact.
PURPOSE: To evaluate and determine Doppler criteria for predicting a severe transplant renal artery stenosis (80%-99% diameter reduction) and to compare the Doppler findings in patients with end-to-end and end-to-side anastomosis. METHODS: We performed Doppler sonography on 16 consecutive patients with transplant renal artery stenosis (TRAS) confirmed by digital subtraction arteriography (DSA). Fourteen patients had end-to-end anastomosis, and 2 had end-to-side anastomosis. Eleven patients were re-evaluated with color Doppler sonography within 4 days after intervention. Seven Doppler parameters, including the peak systolic velocity (PSV) in the renal, iliac and interlobar artery, Pre-PSV ratio (the ratio of the PSV in the renal artery to that in the iliac artery), Post-PSV ratio (the ratio of the PSV in the renal artery to that in the interlobar arteries, acceleration time and resistance index, were measured. In the patients with severe TRAS the measurements of these parameters were compared before and after successful intervention. RESULTS: In the 16 patients with a single transplanted kidney, arteriography demonstrated 14 main renal arteries with severe stenosis, and 3 renal arteries with moderate stenosis. When using the cutoff values of Post-PSV ratio >13, renal artery PSV >4 m/sec, acceleration time >0.06 second, and resistance index <0.5 for the detection of all 14 severe stenoses, the sensitivities were 100%, 71%, 93%, and 50%, respectively. For assessing all 14 severe stenoses and 12 severe stenoses of end-to-end anastomosis, the cutoff value of Pre-PSV ratio >5 had sensitivities of 86% and 100%, respectively. Pre-PSV ratios in severe stenoses of end-to-end anastomosis (range, 5.1-11.5) were significantly greater than those recorded in severe stenoses of end-to-side anastomosis (range, 2.8-3.1). Statistically significant differences before and after successful intervention were found for all 7 Doppler parameters in the 7 patients with severe stenosis. CONCLUSIONS: An 80%-99% diameter reduction of the renal artery can be diagnosed based on a Post-PSV ratio >13 for patients with either end-to-end or end-to-side anastomosis. A Pre-PSV ratio >5 for patients with end-to-end anastomosis and acceleration time >0.06 second are helpful in the diagnosis of severe TRAS.