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Biomedical subjects

Jia Li

Publications and source records attributed to Jia Li.

At least 109 records · Page 6Linked to original sources

[Evaluation of operation and anesthesia on hemodynamic variables in patients undergoing elective abdominal surgery by noninvasive thoracic bioimpedance technique].

OBJECTIVE: To analyse and discuss the effects of elective abdominal operation and anaesthesia on patients' cardiac output via noninvasive thoracic bioimpedance technique. METHODS: Noninvasive monitoring system HeMo-601 was applied to detect the hemodynamic variables of 32 elective abdominal surgery patients. The clinical data of cardiac output (CO), cardiac index (CI), cardiac working per minute (CW), left ventricular end-diastolic pressure (LVEDP), stroke volume (SV), cardiac stroke working (SW) and heart rate (HR) were analysed at 1 hour before operation, 4-6 hours after operation and 24 hours after operation, respectively. RESULTS: No significant differences were found in CO, CI, CW and LVEDP between various time points and preoperation (all P>0.05). SV and SW at 4-6 hours after operation were significant lower than those before operation (all P<0.05). Whereas, SV and SW at 24 hours after operation were no significant differences compared with those before operation (all P>0.05). As compared with preoperation, HR at 4-6 hours after operation was significantly faster (P<0.05). However, there was no significant difference in HR between 24 hours after operation and preoperation (P>0.05). CONCLUSION: The reductions in SV and SW at 4-6 hours after operation might be a result of anaesthesia that could weaken the contraction of heart. The presence of rapidness of HR at 4-6 hours after operation might be a compensatory mechanism for the decreases in SV and SW. Therefore, optimizing adequate infusion by the greatest extent during and after operation is very crucial for the maintenance of CO, CI and tissue perfusion.

Abdomen↗

[Study of operative procedures of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction].

OBJECTIVE: To explore the procedures and the clinical significance of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction. METHODS: Nine cases were assigned randomly to laparoscopically assisted sigmoid colpopoiesis and laparoscopic sigmoid colon colpopoiesis. The procedure of laparoscopically assisted sigmoid colpopoiesis: with the auxiliary of laparoscopy, dissected the distal portion of the sigmoid with endoscopic linear cutter, then a 4-cm incision was made in the left lower abdomen to retract and dissect the proximal portion of sigmoid. After the proximal portion of transplant-sigmoid was closed, the proximal cut end of reserved-sigmoid was placed with the anvil and made a purse-string suture, then put back sigmoid into the peritoneal cavity. A curved intraluminal stapler was inserted from the anus to the most distal cut end of reserved-sigmoid to end-end anastomose the reserved-sigmoid. Finally, an artificial canal was made between urethravesicae and rectum and the transplant-sigmoid with the blood supply was placed into the artificial canal to create an artificial vagina. The procedure of laparoscopic sigmoid colpopoiesis was performed under laparoscopy thoroughly. RESULTS: We have successfully completed the operations for 9 patients, and made 1 - 19 month following-up. The results of the artificial vaginae of all cases were satisfactory; the abdominal scar was small with remarkable cosmetic effects. Moreover, 5 cases had pleasant sexual intercourses. CONCLUSION: The procedures of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction can replace the traditional laparotomy.

Adolescent↗

Type I methionine aminopeptidase from Saccharomyces cerevisiae is a potential target for antifungal drug screening.

AIM: To screen antifungal drug candidates using in vitro and in vivo assays based on type I methionine aminopeptidase from Saccharomyces cerevisiae (ScMetAP1). METHODS: A colorimetric assay suitable for high throughput screening (HTS) using recombinant ScMetAP1 protein expressed in Escherichia coli was established for antifungal lead discovery. A series of pyridine-2-carboxylic acid derivatives were characterized and a chemical library of 12,800 pure organic compounds was screened with the in vitro ScMetAP1 assay. Active compounds from the in vitro assay were further evaluated by a growth inhibition assay on yeast strain with deletion of ScMetAP1 gene map1 in comparison with the wild-type yeast strain and the yeast strain with deletion of type II enzyme (ScMetAP2) gene map2. RESULTS: Active ScMetAP1 inhibitors were identified from HTS. Some of the pyridine-2-carboxylic acid derivatives (compound 2 and 3) had selective inhibition of the growth of map2 deletion yeast and weak inhibition on wild-type yeast growth, while no inhibition on map1 deletion yeast. CONCLUSION: ScMetAP1 is a novel potential target for developing antifungal drugs. The in vitro and in vivo ScMetAP1 assays can serve as tools in discovering antifungal drug candidates.

Aminopeptidases↗

[Indole butyric acid activates Ca2+-ATPase in Malus hupehensis Rhed. roots by protein phosphorylation].

The effect of IBA on protein kinase and Ca(2+)-ATPase activity of Malus hupehensis Rhed. roots were studied by adding 3, 3', 4', 5, 7-pentahydroxyflavone (quercetin), a protein kinase inhibitor, and IBA into the Hagland nutrient solution at different time. The results showed that membrane protein phosphorylation in roots occurred mainly on the serine residues. After treatment of Malus hupehensis Rhed.roots with 100 mumol/L IBA, the activity of protein kinase and Ca(2+)-ATPase increased several dozens of times in 2-3 h and then decreased rapidly after they reached the vertex. The protein kinase activity changes earlier than that of Ca(2+)-ATPase. Quercetin not only inhibits the protein kinase activity, but also weakens the activation of Ca(2+)-ATPase by IBA markedly. It is suggested that Ca(2+)-ATPase may be a member of IBA signal transduction in M. hupehensis roots and IBA activates Ca(2+)-ATPase activity through protein phosphorylation.

Calcium-Transporting ATPases↗

Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease.

BACKGROUND: Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra) in pre- and postoperative children with increased PVR because of CHD. METHODS AND RESULTS: 12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3+/-1.0 Wood Units*m2) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (FiO2=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, P<0.05, and 25.8% versus 14.6% in the post op patient group, P=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Qs/Qt=16.5+/-4.7% to 25.5+/-18.2% P=0.04). CONCLUSIONS: Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.

3',5'-Cyclic-GMP Phosphodiesterases↗

Coexistence of pathogens in sexually-transmitted disease models.

We present a sexually-transmitted disease (STD) model for two strains of pathogen in a one-sex, heterogeneously-mixing population, where the dynamics are of SIS (susceptible/infected/susceptible) type, and there are two different groups of individuals. We analyze all equilibria for the case where contacts are modeled via proportionate (random) mixing. We find that both strains may under suitable circumstances coexist, and that it is the heterogeneous mixing that creates "refuges" for each strain as each population group favors one particular strain.

Animals↗

Specificity for inhibitors of metal-substituted methionine aminopeptidase.

Methionine aminopeptidases (MetAPs) have been studied in vitro as Co(II) enzymes, but their in vivo metal remains to be defined. While activation of Escherichia coli MetAP (EcMetAP1) by Co(II), Mn(II), and Zn(II) was detectable by a colorimetric Met-S-Gly-Phe assay, significant activation by Ni(II) was shown in a fluorescence Met-AMC assay, in addition to Co(II) and Mn(II) activation. When tested on the metal-substituted EcMetAP1s, a few inhibitors that we obtained recently from a random screening on Co-EcMetAP1 either became much weak or lost activity on Mn- or Zn-EcMetAP1, although they kept inhibitory activity on Ni-EcMetAP1. A couple of peptidic inhibitors and the methionine mimetic (3R)-amino-(2S)-hydroxyheptanoic acid (AHHpA, 6) maintained moderate activities on Co-, Mn-, Zn-, and Ni-EcMetAP1s. Our results clearly demonstrate that the metal-substitution has changed the enzyme specificity for substrates and inhibitors. Therapeutic applications call for inhibitors specific for MetAP with a physiologically relevant metal at its active site.

Aminopeptidases↗

Discovery and structural modification of inhibitors of methionine aminopeptidases from Escherichia coli and Saccharomyces cerevisiae.

A series of pyridine-2-carboxylic acid derivatives were synthesized according to the leads from the screening, and potent inhibitors have been obtained by structural modification. They have shown submicromolar inhibition of the enzymes (for example, for 9n, IC(50) = 130 nM for EcMetAP1 and IC(50) = 380 nM for ScMetAP1). They represent small-molecule MetAP inhibitors with novel structures different from alkylating fumagillin derivatives and peptidic bestatin-based MetAP inhibitor.

Aminopeptidases↗

Noninvasive assessment of left ventricular force-frequency relationships using tissue Doppler-derived isovolumic acceleration: validation in an animal model.

BACKGROUND: We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of right ventricular contractile function. In this study, we assessed the usefulness of IVA to measure left ventricular (LV) contractile function and force-frequency relationships in an experimental preparation. METHODS AND RESULTS: In study 1, we examined 6 pigs by use of tissue Doppler imaging of LV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (Emax), and dP/dtmax by conductance catheterization. Animals were paced via the right atrium at a rate of 130 bpm. IVA was compared with elastance during contractility modulation by esmolol and dobutamine and assessed during preload reduction and afterload increase. In study 2, in 6 more pigs, force-frequency data were obtained during incremental atrial pacing from 120 to 180 bpm. Study 1: Esmolol led to a decrease in IVA and Emax (P<0.03 and <0.02, respectively), both of which increased during dobutamine infusion (P<0.02 and <0.03, respectively). IVA was unaffected by significant (P<0.001) acute reduction of LV volume and a significantly increased LV afterload (systolic pressure increase, P<0.001). Study 2: There was a positive correlation between IVA and dP/dtmax (r2=0.92, P<0.05). As heart rate was increased from 120 to 160 bpm, there were significant increases in both IVA and dP/dtmax (P<0.0004 and P=0.02, respectively). Over the same range of heart rates, there was no significant change in Emax (P=0.22). CONCLUSIONS: IVA is a measurement of LV contractile function that is unaffected by preload and afterload changes within a physiological range and can be used noninvasively to measure LV force-frequency relationships.

Animals↗

Modeling the impact of random screening and contact tracing in reducing the spread of HIV.

Mathematical models can help predict the effectiveness of control measures on the spread of HIV and other sexually transmitted diseases (STDs) by reducing the uncertainty in assessing the impact of intervention strategies such as random screening and contact tracing. Even though contact tracing is one of the most effective methods used for controlling treatable STDs, it is still a controversial strategy for controlling HIV because of cost and confidentiality issues. To help estimate the effectiveness of these control measures, we formulate two models with random screening and contact tracing based on the differential infectivity (DI) model and the staged-progression (SP) model. We derive formulas for the reproductive numbers and the endemic equilibria and compare the impact that random screening and contact tracing have in slowing the epidemic in the two models. In the DI model the infected population is divided into groups according to their infectiousness, and HIV is largely spread by a small, highly infectious, group of superspreaders. In this model contact tracing is an effective approach to identifying the superspreaders and has a large effect in slowing the epidemic. In the SP model every infected individual goes through a series of infection stages and the virus is primarily spread by individuals in an initial highly infectious stage or in the late stages of the disease. In this model random screening is more effective than for the DI model, and contact tracing is less effective. Thus the effectiveness of the intervention strategy strongly depends on the underlying etiology of the disease transmission.

Contact Tracing↗

Doppler tissue echocardiography: can transesophageal echocardiography be used to acquire functional data?

BACKGROUND: To date there is no direct comparison of transesophageal and transthoracic Doppler tissue data in patients with cardiac malposition. We compared data acquired from both methods in an animal model. METHOD: We studied 10 15-kg Yorkshire pigs during incremental atrial pacing to modify myocardial responses. Peak isovolumic velocity (IVV) and isovolumic acceleration (IVA) during isovolumic contraction, ejection (S wave), and diastolic velocities (early passive and active filling, E and A wave, respectively) were measured. RESULTS: Bland-Altman plots showed comparable values for IVA, IVV, and E velocity using both methods. Measurements of A velocities were significantly different. S wave velocity measurements were significantly different in animals with cardiac malposition but not in those with levocardia. Malposition did not significantly effect measurements of IVA or IVV by either technique. CONCLUSION: Assessment of systolic function using the indices IVA and IVV by tranesophageal and transthoracic echocardiography are comparable. The tranesophageal assessment of velocities associated with greater degrees of myocardial shortening or lengthening cannot be directly compared with measurements derived from a transthoracic approach in patients with cardiac malposition.

Animals↗

New insights into the function and regulation of endothelial cell apoptosis.

The sculpting of blood vessels to meet the changing requirements of the tissues they supply is essential for life. Many researchers believe that endothelial cell apoptosis plays an important role in this process. This belief is bolstered by the detection of endothelial apoptosis within remodeling vessels in vivo, the dramatic vascular phenotypes of mice in which regulators of endothelial apoptosis have been inactivated and the apparent dependence of angiogenesis on endothelial apoptosis in vitro. However, when examined carefully, the evidence for or against endothelial cell apoptosis playing an important role in vascular biology is largely indirect and is far from clear-cut. In this review, we will discuss the idiosyncratic process of endothelial cell apoptosis. We will then examine its complex regulation and weigh the in vitro and in vivo evidence that it plays a significant role in mammalian vascular biology.

Animals↗

Significance of interspecies matches when evolutionary rate varies.

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be sufficiently similar that some but not all of the neutrally evolving regions (i.e., those under no evolutionary constraint) can be reliably aligned. Our goal is to model the situation in which the neutral rate of evolution, and hence the extent of the aligning intervals, varies across the genome. In some cases, this permits the weaker of two matches to be judged as less likely to have arisen by chance, provided it lies in a genomic interval with a high level of background divergence. We employ a hidden Markov model to capture variations in divergence rates and assign probability values to gap-free alignments using techniques of Dembo and Karlin, which are related to those used for the same purpose by BLAST. Our methods are illustrated in detail using a 1.49 Mb genomic region. Results obtained from the analysis of human chromosome 22 using these techniques are also provided.

Animals↗

Measured versus estimated oxygen consumption in ventilated patients with congenital heart disease: the validity of predictive equations.

OBJECTIVE: To determine the validity of predictive equations in calculating oxygen consumption (Vo(2)) in ventilated patients with congenital heart disease. DESIGN: Prospective study. SETTING: Cardiac catheterization laboratories and intensive care units of two university teaching hospitals. PATIENTS: A total of 126 patients with congenital heart disease were studied. Of these, 75 patients received anesthesia in the pediatric cardiac catheterization laboratory, and 51 were deeply sedated in the intensive care unit after open heart surgery. MEASUREMENTS AND MAIN RESULTS: Vo(2) was measured directly in all patients using respiratory mass spectrometry. Estimated values for absolute Vo(2) (mL/min) and indexed Vo(2) (mL.min-1.m-2) were calculated from the four predictive equations published by LaFarge and Miettinen, Lundell et al., Wessel et al., and Lindahl. The agreement between measured and estimated Vo(2) was evaluated by calculating their bias and limits of agreement. A failure of agreement between measured and estimated Vo(2) was noted in both groups of patients, irrespective the equation used, and the agreement was poorer in patients in the intensive care unit. The equation by LaFarge and Miettinen produced the closest estimation in patients at cardiac catheterization with a bias of 4.5 mL/min for absolute Vo(2) and 6.9 mL.min-1.m-2 for indexed Vo(2). A systematic error of overestimating lower and underestimating higher indexed Vo(2) mL.min-1.m-2 was introduced in both groups. CONCLUSION: Predictive equations do not accurately estimate Vo(2) in ventilated patients with congenital heart disease.

Adolescent↗

Distinguishing regulatory DNA from neutral sites.

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human-mouse genomic alignments were collected for three sets of human regions: (1) experimentally defined gene regulatory regions, (2) well-characterized exons (coding sequences, as a positive control), and (3) interspersed repeats thought to have inserted before the human-mouse split (a good model for neutrally evolving DNA). Models that potentially could distinguish functional noncoding sequences from neutral DNA were evaluated on these three data sets, as well as bulk genome alignments. Our analyses show that discrimination based on frequencies of individual nucleotide pairs or gaps (i.e., of possible alignment columns) is only partially successful. In contrast, scoring procedures that include the alignment context, based on frequencies of short runs of alignment columns, dramatically improve separation between regulatory and neutral features. Such scoring functions should aid in the identification of putative regulatory regions throughout the human genome.

Animals↗

Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution.

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of (1) nucleotide substitution per fourfold degenerate site in coding regions, (2) nucleotide substitution per site in relics of transposable elements active only before the human-mouse speciation, and (3) the nonaligning fraction of human DNA that is nonrepetitive or in ancestral repeats; and three derived from human genome data alone, consisting of (4) SNP density, (5) frequency of insertion of transposable elements, and (6) rate of recombination. Features 1 and 2 are measures of nucleotide substitutions at two classes of "neutral" sites, whereas 4 is a measure of recent mutations. Feature 3 is a measure dominated by deletions in mouse, whereas 5 represents insertions in human. It was found that all six vary significantly in megabase-sized regions genome-wide, and many vary together. This indicates that some regions of a genome change slowly by all processes that alter DNA, and others change faster. Regional variation in all processes is correlated with, but not completely accounted for, by GC content in human and the difference between GC content in human and mouse.

Animals↗