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Biomedical subjects

J Shen

Publications and source records attributed to J Shen.

At least 451 records · Page 25Linked to original sources
PubMed1993

Regulation of adenine nucleotide concentration at endothelium-fluid interface by viscous shear flow.

The action of adenine nucleotides on vascular endothelial cells is apparently mediated by the local flow conditions. Because nucleotides are sequentially degraded from ATP-->ADP-->AMP-->adenosine by ecto-enzymes at the endothelial surface, it has been hypothesized that the observed flow effect is caused by the flow-dependent change of nucleotide concentration at the cell surface. In this study, we have calculated the concentration profiles of adenine nucleotides at the cell surface under flow conditions encountered in an in vitro parallel-plate flow system, as has been used in several related experimental studies. When medium containing uniformly distributed ATP is perfused over endothelial monolayers, our results show that ATP concentration in the cell vicinity gradually decreases in the streamwise direction as a result of enzymatic degradation. This hydrolysis of ATP results in the generation of ADP, and ADP concentration in turn gradually increases at the cell surface. The concentration profiles of nucleotides are dependent on the levels of applied wall shear rate. As the corresponding shear stress increases from 0.1 to 30 dynes/cm2, ATP concentration at the cell surface at the center of coverslip increases from 0.66 to 0.93. Under no-flow conditions, our model predicts a steady decline of ATP concentration and a transient increase of ATP-derived ADP, comparable to the published results of previous experiments. These numerical results, combined with our recent experimental data, provide insights into the cellular mechanisms by which hemodynamic flow modulates the effects of vasoactive agents on endothelium.

Adenine Nucleotides↗
PubMed1993

Locus-specific variation in phosphorylation state of RNA polymerase II in vivo: correlations with gene activity and transcript processing.

To investigate functional differences between RNA polymerases IIA and IIO (Pol IIA and Pol IIO), with hypo- and hyperphosphorylated carboxy-terminal repeat domains (CTDs), respectively, we have visualized the in vivo distributions of the differentially phosphorylated forms of Pol II on Drosophila polytene chromosomes. Using phosphorylation state-sensitive antibodies and immunofluorescence microscopy with digital imaging, we find Pol IIA and Pol IIO arrayed in markedly different, locus- and condition-specific patterns. Major ecdysone-induced puffs, for example, stain exclusively for Pol IIO, indicating that hyperphosphorylated Pol II is the transcriptionally active form of the enzyme on these genes. In striking contrast, induced heat shock puffs stain strongly for both Pol IIA and Pol IIO, suggesting that heat shock genes are transcribed by a mixture of hypo- and hyperphosphorylated forms of Pol II. At the insertion sites of a transposon carrying a hybrid hsp70-lacZ transgene, we observe only Pol IIA before heat shock induction, consistent with the idea that Pol II arrested on the hsp70 gene is form IIA. After a 90-sec heat shock, we detect heat shock factor (HSF) at the transposon insertion sites; and after a 5-min shock its spatial distribution on the induced transgene puffs is clearly resolved from that of Pol II. Finally, using antibodies to hnRNP proteins and splicing components, we have discerned an apparent overall correlation between the presence and processing of nascent transcripts and the presence of Pol IIO.

Amino Acid Sequence↗
PubMed1993

A clinical trial of a slow-release formulation of acetylsalicylic acid in patients at risk for preeclampsia.

The formation of thromboxane A2 (TXA2) in maternal and foetal cord serum was measured at birth in eight control patients and in 13 patients taking 100 mg of a slow-release formulation of acetylsalicylic acid. The serum concentrations of TXB2 (a stable end product of TXA2 hydrolysis) in both maternal and cord serum from patients who ingested the acetylsalicylic acid formulation were significantly lower (P < 0.01) than those in control subjects. Acetylsalicylic acid was not detected (< 30 ng ml-1) in maternal plasma from six mothers and in cord plasma from seven foetuses in the acetylsalicylic acid-treated group. The mean cord to maternal plasma concentration ratios for detectable acetylsalicylic acid and salicylate were 0.62 +/- 0.19 (s.d.) (n = 6) and 0.84 +/- 0.16 (n = 13), respectively. We conclude that low doses of acetylsalicylic acid given in a slow-release form to mothers during pregnancy cause depression of TXA2 formation in the foetal blood.

Adult↗
PubMed1993

Tissue-specific alternative splicing of the Drosophila dopa decarboxylase gene is affected by heat shock.

The Drosophila dopa decarboxylase gene, Ddc, is expressed in the hypoderm and in a small number of cells in the central nervous system (CNS). The unique Ddc primary transcript is alternatively spliced in these two tissues. We investigated whether Ddc splicing in the CNS is a general property of the CNS or a unique property of the cells that normally express Ddc by expressing the Ddc primary transcript ubiquitously under the control of an Hsp70 heat shock promoter. Under basal expression conditions, Ddc splicing shows normal tissue specificity, indicating that the regulation of Ddc splicing in the CNS is tissue specific rather than cell specific. Previous studies have shown that severe heat shock blocks mRNA splicing in cultured Drosophila melanogaster cells. Our results show that splicing of the heat shock-inducible Hsp83 transcript is very resistant to heat shock. In contrast, under either mild or severe heat shock, the splicing specificity of the heat shock-induced Ddc primary transcript is affected, leading to the accumulation of inappropriately high levels of the CNS splice form in non-CNS tissues. The chromosomal Ddc transcript is similarly affected. These results show unexpected heterogeneity in the splicing of individual mRNAs as a response to heat shock and suggest that the Ddc CNS-specific splicing pathway is the default.

Alternative Splicing↗
PubMed1993

Immunologic abnormalities in children with acute Kawasaki disease.

Spontaneous release of IgG, production of IgG, IgM and IgG subclasses induced by PWM in vitro, serum IgG, IgM, IgA and IgG subclasses were measured in 23 patients with acute Kawasaki disease (KD). The results showed that there was polyclonal B cell activation with significantly increased IgG1 and IgG3. As compared with 21 healthy controls, the mean activities of B cell growth factors (BCGFs), B cell differentiation factors (BCDFs) and interleukin 6 (IL-6) were significantly elevated. IL-6 activity was correlated with the production of IgG, IgG1, IgG3 and IgM, while BCGFs and BCDFs were also correlated with IgG1. The serum level of circulating tumor necrosis factor (TNF) determined in 16 patients with acute KD using double antibody ELISA was 1.86-8.83 micrograms/ml, but it was less than 1 microgram/L in normal controls. The clinical value of increased TNF in serum is discussed.

Child↗
PubMed1993

Clinical and experimental studies on shallow needling technique for treating childhood diarrhea.

Treatment of diarrhea in children by shallow needling and by drugs was studied in 3 separate groups for comparison. For Group I, the lateral line II of the forehead was taken, i.e. the upper, middle and lower points of the line staring from Toulinqi (UB 15) vertically downwards to the place 1 cm below the hairline were selected. For Group II, shallow needling was done on body acupoints, the main points selected being Qihai (Ren 6), Shuifen (Ren 9), bilateral Tianshu (St 25), and bilateral Zusanli (St 36); the adjuvant acupoints were Taibai (Sp 3) and Gongsun (Sp 4). The depth of shallow needling was merely puncturing the skin. For Group III the drugs used were Liteling, Berberine, Gentamycin, Ampicillin, and SMZ Co. The results of treatment in Group I and II differed insignificantly, while both were significantly superior to drugs in Group III. Experimental studies also showed that shallow needling enhanced the humoral and cellular immunity and promoted the intestinal peristaltic function.

Acupuncture Therapy↗
PubMed1992

Epidermal growth factor-induced survival and proliferation of neuronal precursor cells from embryonic rat mesencephalon.

Neuronal and glial precursor cells were isolated from primary cultures of embryonic rat mesencephalon. The separation of precursor cells from the neurons was accomplished by the resuspension of the primary cells by trypsinization, followed by replating. This procedure resulted in the death of differentiated neurons and the survival of precursor cells. The survival and proliferation of the replated precursor cells required the presence of epidermal growth factor (EGF) in the culture medium. The precursor cells differentiated into neurons and astrocytes, as determined by immunocytochemical staining with antibodies to neuron specific enolase (NSE) and tau protein or glial fibrillary acidic protein (GFAP) respectively.

Animals↗
PubMed1992

Is age an independent predictor of early and late mortality in patients with acute myocardial infarction?

PURPOSE: To determine whether advancing age is an independent predictor of increased mortality following acute myocardial infarction or simply a marker for more extensive cardiac disease, a higher prevalence of comorbid conditions, and/or differences in therapeutic approach. PATIENTS: A total of 261 consecutive patients with documented acute myocardial infarction admitted to a university teaching hospital during a 1-year interval. METHODS: Seventy-four variables were analyzed to determine univariate predictors of inhospital and 1-year post-discharge mortality. Multiple linear regression models were constructed to determine independent predictors of early and late mortality after adjusting for baseline and therapeutic differences between younger and older patients. RESULTS: Compared with patients less than 70 years (n = 124), patients greater than or equal to 70 years (n = 137) were more likely (all p less than 0.05) to be female and have a prior history of ischemic heart disease. New York Heart Association functional class and Killip class on admission were higher in older patients, as were the admission serum creatinine and blood urea nitrogen levels. Serum albumin and peak creatine kinase levels were lower in older patients, but older patients were more likely to exhibit left ventricular hypertrophy or atrioventricular block on the initial electrocardiogram. Finally, younger patients were three times as likely to receive a thrombolytic agent and 66% more likely to receive intravenous beta-blockade than older patients, and younger patients were also more likely to receive heparin and intravenous nitroglycerin. Hospital mortality was 5.6% in patients less than 70 years versus 16.1% in patients greater than or equal to 70 years (p = 0.013). After adjusting for baseline and therapeutic differences, independent predictors of hospital mortality were systolic blood pressure on admission (inverse correlation, p = 0.0095), beta-blocker therapy (inverse correlation, p = 0.01), age (p = 0.014), peak creatine kinase level (p = 0.015), and Killip class (p = 0.035). Among hospital survivors, 1-year post discharge mortality was 6.8% in patients less than 70 years versus 19.1% in those greater than or equal to 70 years (p = 0.001). Independent predictors of post-discharge mortality after adjusting for age-related baseline and therapeutic differences were admission heart rate (p = 0.0004), age (p = 0.011), left ventricular ejection fraction (inverse correlation, p = 0.012), initial non-Q-wave myocardial infarction (p = 0.026), and the blood urea nitrogen level (p = 0.036). CONCLUSION: After adjusting for multiple baseline and therapeutic differences between older and younger patients, age per se remains a strong independent predictor of both inhospital and 1-year post-discharge mortality rates in patients with acute myocardial infarction.

Age Factors↗
PubMed1992

Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells.

Cytosolic free Ca2+ concentration ([Ca2+]i) was monitored in single and groups of fura-2-loaded bovine aortic endothelial cells (BAEC) during exposure to laminar fluid shear stress. Application of a step increase in shear stress from 0.08 to 8 dyn/cm2 to confluent BAEC monolayers resulted in a transient increase in [Ca2+]i, which attained a peak value in 15-40 s, followed by a decline to baseline within 40-80 s. The magnitude of the [Ca2+]i responses increased with applied shear stress over the range of 0.2-4 dyn/cm2 and reached a maximum at greater than 4 dyn/cm2. Transient oscillations in [Ca2+]i with gradually diminishing amplitude were observed in individual cells subjected to continuous high shear stress. Elimination of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, blockade of Ca2+ entry with lanthanum, depolarization of the cell membrane with high K+, and preconditioning of BAEC in steady laminar flow had little effect on the [Ca2+]i response. In the presence of ATP or ADP, application of shear stress caused repetitive oscillations in [Ca2+]i in single BAEC, whose frequency was dependent on both agonist concentration and the magnitude of applied shear stress. However, apyrase, an ATPase and ADPase, did not inhibit the shear-induced [Ca2+]i responses in standard medium (no added ATP or ADP), suggesting that the shear-induced [Ca2+]i response is not due to ATP released by endothelial cells.

Adenosine Triphosphate↗
PubMed1992

Hemodynamic effects and the effective treatment of naloxone on experimental acute pancreatitis in dogs.

Dog model of acute pancreatitis, induced by intrapancreatoductal injection of fresh trypsin-bile mixture, was used to investigate the effects of naloxone on hemodynamic changes in acute pancreatitis. In the control group, acute pancreatitis was induced and characterized hemodynamically by the decrease in maximum positive and negative dP/dt (+/- dP/dtmax), cardiac output (CO) and cardiac index (CI), and increase in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVP), as well as early reduction of pancreatic blood flow (PBF). In the naloxone treated group, naloxone was given intravenously 10 minutes after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 hours). It was found that naloxone significantly increased PBF and the +/- dP/dtmax effectively prevented the significant decrease in CO, CI and increase in PVR, SVR observed in untreated acute pancreatitis; and significantly reduced the severity of pancreatitis, as assessed by both histological staging and mortality rate. These results suggest that naloxone appears to limit the progression from edematous to hemorrhagic pancreatitis through preserving PBF and improving systemic hemodynamics at the early phase of acute pancreatitis; hence the hypothesis that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis.

Acute Disease↗
PubMed1991

Model representation of salicylate pharmacokinetics using unbound plasma salicylate concentrations and metabolite urinary excretion rates following a single oral dose.

The pharmacokinetics of salicylic acid (SA) and its metabolites have been studied in 5 volunteers after administration of 3 g salicylic acid (as sodium salicylate) and collection of serial samples of blood and urine. SA and its metabolites were assayed with a HPLC method specific for each species. The urinary excretion rates of individual metabolites were analyzed using unbound plasma SA concentrations and Lineweaver-Burke plots. The analysis confirmed that the formation of SA urate (SU) and SA phenolic glucuronide (SPG) metabolites are saturable processes, and showed that the Michaelis-Menten values derived are consistent with earlier estimates derived solely from urinary data. The unbound salicylate plasma concentration-time profiles were then analyzed with various models assuming either saturable clearances for metabolite formation and/or saturable protein binding. The data were best described with a model that included both saturable protein binding and saturable metabolism. The model assumed first-order absorption kinetics and instantaneous distribution into extravascular and tissue compartments. The model was validated by comparing predicted relationships between the apparent volume of distribution, clearance, and plasma salicylate concentrations with previous relationships obtained using steady state data.

Administration, Oral↗
PubMed1991

Photoacoustic study of iron-deficiency anaemia.

A photoacoustic spectrum of a smear of whole blood clearly shows all of the details of the haem absorption in an optical spectrum and good optical absorption data without a data extraction procedure. There are three peaks; gamma (420 nm), beta (550 nm), and alpha (585 nm) in the band 350-700 nm. For iron-deficiency anaemia the peak/peak ratios, ratios of the value of peak gamma to that of the peak beta and peak alpha, and the integral/integral ratios, ratios of the value of the integral under the peak gamma to that under the peak beta, peak alpha, peak beta and peak alpha are closely related to the variation of haemoglobin concentration. Linear relationships among the ratios and the Hb concentration are found. These ratios could be a good index of haem synthesis disturbance.

Anemia, Hypochromic↗