Search PubMed⌕ Search

Biomedical subjects

P Li

Publications and source records attributed to P Li.

At least 181 records · Page 10Linked to original sources
PubMed2000

Endogenous nitric oxide mediates pancreatic exocrine secretion stimulated by secretin and cholecystokinin in rats.

Nitric oxide (NO) is one of the important biologic mediators in regulation of gastrointestinal (GI) functions, but the influence of NO on the release of secretin and cholecystokinin (CCK) and exocrine pancreatic secretion has not been adequately investigated in the rat. The aim of this study was to determine the role of NO on endogenous and exogenous secretin- or CCK-stimulated pancreatic exocrine secretion both in anesthetized and conscious rats. Experiments were carried out in four different groups of rats with duodenal pancreatobiliary cannulas and jugular vein catheters. Group 1: During duodenal infusion of 0.05N HCl or 15% casein (pH 7.0), N-nitro-L-arginine (NNA), an inhibitor of NO-synthase in graded doses (2.5, 5, 10 mg/kg/h), was infused intravenously. Group 2: One hour after starting intravenous secretin at 5 pmol/kg/h or intravenous CCK-8 at 0.06 microg/kg/h, NNA in graded doses was administered intravenously. Group 3: In conscious rats, NNA (5 mg/kg/h) was given intravenously for 1 hour after a meal. Group 4: L-Arginine at 100 mg/kg/h was infused intravenously during the period of NNA (5 mg/kg/h) infusion in groups 1, 2, and 3. Pancreatic juice was collected at 30-minute intervals to measure volume, as well as output of bicarbonate and protein. At the end of the experiment, plasma secretin, vasoactive intestinal polypeptide (VIP) and CCK levels were determined by radioimmunoassay (RIA). NNA dose dependently inhibited the pancreatic secretion of fluid and bicarbonate stimulated by duodenal acidification, exogenous secretin, and a meal. NNA dose dependently inhibited the pancreatic secretion of protein stimulated by duodenal infusion of casein, exogenous CCK, and a meal. L-Arginine significantly reversed the NNA-induced inhibition of pancreatic secretion in all experiments. NNA did not alter significantly the plasma levels of secretin, VIP, and CCK. Our results indicated that endogenous NO plays a significant role in the regulation of pancreatic exocrine secretion stimulated by secretin and CCK. However, NO does not influence the release of secretin, VIP, or CCK in the rat.

Animals↗
PubMed2000

An immunohistochemical analysis of p27 expression in human pancreatic carcinomas.

p27 is known as one of the candidate tumor suppressor genes. Although abnormalities including deletion and mutation in this gene are rarely detected, loss of p27 expression has been reported to be correlated with the high degree of malignancy in many human cancers. In the present study, we investigated the status of p27 expression in human pancreatic carcinoma (PC) and assessed the clinicopathologic significance of loss of p27 expression in the development and progression of this malignancy using immunohistochemistry. No nuclear staining for p27 protein existed in 65 (65.7%) of the 99 PC tumors examined. Furthermore, loss of p27 expression was correlated with tumor grade (G1 versus G2 or G3, p < 0.05) or clinical stage (I and II versus III and IV, p < 0.01). The above data suggest that loss of p27 expression is a very common event in PC, and moreover, this alteration might contribute to the progression of this malignant disease. Key Words: Pancreatic carcinoma-p27 protein expression-Immunohistochemistry.

Cell Cycle Proteins↗
PubMed2000

Inhibition of gastric acid secretion in rat stomach by PACAP is mediated by secretin, somatostatin, and PGE(2).

Pituitary adenylate cyclase-activating polypeptide (PACAP), existing in two variants, PACAP-27 and PACAP-38, is found in the enteric nervous system and regulates function of the digestive system. However, the regulatory mechanism of PACAP on gastric acid secretion has not been well elucidated. We investigated the inhibitory action of PACAP-27 on acid secretion and its mechanism in isolated vascularly perfused rat stomach. PACAP-27 in four graded doses (5, 10, 20, and 50 microg/h) was vascularly infused to determine its effect on basal and pentagastrin (50 ng/h)-stimulated acid secretion. To study the inhibitory mechanism of PACAP-27 on acid secretion, a rabbit antisecretin serum, antisomatostatin serum, or indomethacin was administered. Concentrations of secretin, somatostatin, PGE(2), and histamine in portal venous effluent were measured by RIA. PACAP-27 dose-dependently inhibited both basal and pentagastrin-stimulated acid secretion. PACAP-27 at 10 microg/h significantly increased concentrations of secretin, somatostatin, and PGE(2) in basal or pentagastrin-stimulated state. The inhibitory effect of PACAP-27 on pentagastrin-stimulated acid secretion was reversed 33% by an antisecretin serum, 80.0% by an antisomatostatin serum, and 46.1% by indomethacin. The antisecretin serum partially reduced PACAP-27-induced local release of somatostatin and PGE(2). PACAP-27 at 10 microg/h elevated histamine level in portal venous effluent, which was further increased by antisomatostatin serum. However, antisomatostatin serum did not significantly increase acid secretion. It is concluded that PACAP-27 inhibits both basal and pentagastrin-stimulated gastric acid secretion. The effect of PACAP-27 is mediated by local release of secretin, somatostatin, and PGE(2) in isolated perfused rat stomach. The increase in somatostatin and PGE(2) levels in portal venous effluent is, in part, attributable to local action of the endogenous secretin.

Animals↗
PubMed2000

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II.

Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a -/- mice. Plasma vasopressin levels increase normally in the AT(1A) receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT(1)-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

Angiotensin Receptor Antagonists↗
PubMed2000

Nerve growth factor-potentiating compounds from Picrorhizae Rhizoma.

A crude methanol extract of Picrorhizae Rhizoma, the dried underground parts of Picrorhiza scrophulariiflora PENNELL, has been shown to potentiate the nerve growth factor (NGF)-induced neurite outgrowth from PC12D cells. The methanol extract was partitioned between ethyl acetate and water. The NGF-potentiating activity was observed in the ethyl acetate fraction. The ethyl acetate solubles were fractionated by silica gel chromatography, monitoring the NGF-potentiating activity to give two iridoid glycosides, picrosides I and II. Picrosides did not exhibit neurotrophic activity but caused a marked enhancement of the NGF-mediated neurite outgrowth from PC12D cells. The pharmacological data suggest that picrosides I and II enhance neurite outgrowth from PC12D cells, probably by amplifying a step in the NGF-receptor-mediated intracellular signaling pathway.

Animals↗
PubMed2000

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.

Animals↗
PubMed2000

Novel angiotensin II AT(1) receptor antagonist irbesartan prevents thromboxane A(2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation.

This study was conducted to investigate whether the novel orally active nonpeptide angiotensin II (Ang II) AT(1) receptor antagonist irbesartan interacts with the thromboxane A(2)/prostaglandin endoperoxide H(2) (TxA(2)/PGH(2)) receptor in canine coronary arteries and human platelets. Coronary artery rings were isolated from male dog hearts (n = 18) and isometric tension of vascular rings was measured continuously at optimal basal tension in organ chambers. Autoradiographic binding of [(3)H]SQ29,548, a TxA(2) receptor antagonist, in canine coronary sections was determined. Blood for platelet aggregation studies was collected by venous puncture from healthy human volunteers (n = 6) who were free of aspirin-like agents for at least 2 weeks. Vascular reactivity and platelet aggregation in response to the TxA(2) analogs U46619 and autoradioagraphic receptor binding to the TxA(2) receptor antagonist [(3)H]SQ29,548 were studied with and without irbesartan. The TxA(2) analog U46619 produced dose-dependent vasoconstriction in coronary rings (EC(50) = 11.6 +/- 1.5 nM). Pretreatment with irbesartan inhibited U46619-induced vasoconstriction, and the dose-response curve was shifted to the right in a dose-dependent manner. The EC(50) of U46619 was increased 6- and 35-fold in the presence of 1 and 10 microM of irbesartan without a change of maximal contraction. At 1 microM, irbesartan is 2-fold more potent than the AT(1) receptor antagonist losartan in the inhibition of U46619-induced vasoconstriction in canine coronary arteries. In contrast, neither AT(1) receptor antagonists (CV11974 and valsartan), the AT(2) receptor antagonist PD123319, nor the angiotensin converting enzyme inhibitor lisinopril had any effect on U46619-induced coronary vasoconstriction. Irbesartan did not change potassium chloride-induced vasoconstriction; however, irbesartan did inhibit the vasoconstriction mediated by another TxA(2)/PGH(2) receptor agonist prostaglandin F(2alpha) (PGF(2alpha)). Neither the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin had any effect on irbesartan's attenuation of U46619-induced vasoconstriction. Irbesartan specifically reversed U46619-preconstricted coronary artery rings with and without endothelium in a dose-dependent manner. Irbesartan at high concentrations significantly competed for [(3)H]SQ29,548 binding in canine coronary sections. U46619 stimulated dose-dependent human platelet aggregation of platelet-rich plasma. Preincubation with irbesartan significantly inhibited platelet aggregation in a concentration-dependent manner. In conclusion, the dual antagonistic actions of irbesartan by acting at both the AT(1) and TxA(2) receptors in blood vessels and platelets may overall enhance its therapeutic profile in the treatment of hypertension, atherosclerosis, and arterial thrombosis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

[The common C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with neural tube defects and preeclampsia].

OBJECTIVE: To assess whether methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphism is associated with neural tube defects and preeclampsia. METHODS: Twenty- four mothers who had given birth to normal children, 27 mothers who had given birth to NTDs children, 120 normal women, and 57 women who had suffered from preeclampsia were genotyped for C677T polymorphism by using PCR/RFLP method. RESULTS: (1) VV genotype frequency in the normal mothers group it was 0.13, while in the NTDs mothers group it was 0.33; mothers with VV genotype were at 3 times increased risk to have a NTDs child, compared with the normal mothers. (2) In the normal women group VV genotype frequency was 0.15, while in the preeclampsia women group it was 0.31; women with VV genotype were at 2.5 times increased risk to have preeclampsia, compared with the normal women. CONCLUSION: The authors believe that MTHFR VV genotype is associated with the development of NTDs and preeclampsia.

Female↗
PubMed2000

[Assessment of malaria DNA vaccines in mice and monkeys].

Cholera toxin B subunit is a good carrier protein and an effective adjuvant which can boost both cellular and humoral immunity. DNA fragments encoding B cell, Th cell and CTL epitopes of P. falciparum CS, MSA-1, MSA-2 and RESA antigens were cloned down-2 stream of cholera toxin B subunit gene in the same reading frame. High titer of anti-malaria epitopes antibodies and strong cellular immunogenicity were elicited after Balb/c mice were immunized three times with 100 micrograms recombinant plasmid DNA dissolved in 100 microliters PBS. A total of 120 vaccinees were challenged with mouse Plasmodium yoelli to investigate if cross protection existed. The protective efficacy was about 60%-80%. Four rhesus monkeys were challenged with 10(8) of P. cynomalgi, better results were obtained in the groups immunized with mixed plasmids including NANP, AWTE.

Animals↗
PubMed2000

[The application of fluorescence in situ hybridization performed on the decolorized G-banding chromosomes in detecting the marker chromosomes of gastric cancer].

OBJECTIVE: Using a rapid, accurate method that detects the marker chromosomes of gastric cancer and enhancing the ability of discriminating complicated chromosome rearrangements of gastric cancer. METHODS: The improved method of fluorescence in situ hybridization(FISH) performed on the decolorized G-banding chromosome was used. RESULTS: The changes of two marker chromosomes (M1, M2) of the cell line(SGC-7901) of gastric cancer and one marker chromosomes(M3) of one primary gastric cancer were respectively analyzed by this method. The M1, M2 and M3 had complicated structural chromosome aberrations: del(7)(p15)/del(7)(q22), t(1;3)(p11;q11) and del(7)(q32). CONCLUSION: This method showed strong signals, low backgrounds and well-repetitions. It may play an important part in exploring the chromosome rearrangements in the process of pathogenesis and development of gastric cancer.

Chromosome Aberrations↗
PubMed2000

[Translation initiation function of the regulation element in the operon of cholera toxin A].

To demonstrate that there existed translation coupling between cholera toxin A subunit gene and B subunit gene, and give the answer why the expression level of B gene is five times more than that of A gene, alpha report system for the investigation of translation coupling was constructed by using lacZ gene as reporter. Frame-shift mutation was introduced near the C terminal of ctxA gene, and the ribosome would read through its normal stop codon. The report plasmid was constructed and it was found that the expression level of lacZ gene decreased five times after the frame-shift mutation. The translation of cholera toxin B subunit gene was translational coupled with A subunit gene, and was responsible for the differential expression level of the two genes.

Cholera Toxin↗
PubMed2000

[A new model of translational control of gene expression in polycistron++ of AB5 entrerotoxin].

The expression level of the B subunit gene of cholera toxin (ctx) and E. coli heat labile toxin (ltx) is five to seven times more than that of A subunit gene. In these studies, a 80 basepair translation regulation element was found located in the structure gene of A gene of both toxin operon which consists of three translation initiation region. Site-directed mutation of the initiation codon of TIR3 resulted in the 9 time decrease of the expression of the downstream cistron which was translational coupled with A gene. The results indicated that translation from the internal of A gene and translation coupling are responsible for the differential expression level of the A and B gene of AB5 enterotoxin.

Bacterial Toxins↗
PubMed2000

[Induction of protective immune response in mice and rhesus monkeys by immunization with fusion protein of cholera toxin B subunit and multiples of Plasmodium falciparum].

Recombinant fusion protein of cholera toxin B subunit (CTB) and poly-valent protective epitopes of plasmodium falciparum was given to i.m. to C57BL/6j mice and rhesus monkeys three times. In rhesus monkeys, high level of antibodies for CTB (1:6400) and malaria epitopes (1:3200) amtobpdoes were elicited as well as the specific CTL activity for P. plasmodium. After the mice were challenged with sporozoites of P. yeolli, about 50% of them were protected from the patent infection. A blood-stage challenge with 10(8) of P. cynomolgi parasite were given to rhesus monkeys, which showed that two animals in control group were patent infection for at least 30 days, in contrast, the two animals immunized were recovered respectively at the day of 11 and 15 after challenges. The results suggested that cholera toxin acts as an effective adjuvent in the development of malaria vaccine.

Animals↗
PubMed2000

Distribution of a common methylenetetrahydrofolate mutation in six Chinese population groups.

The distribution of the C677T polymorphism was analyzed by the PCR-RFLP technique in the Northeast Han, the Oroqen, the Ewenki, the Daur as well as in Koreans and Mongolians. The results were compared with each other. They revealed that the frequencies of the T allele are quite different (17-47%) among the tested groups and are much higher in Chinese population groups than in others.

Asian People↗
PubMed2000

Analysis of DYS19 and DYS287 polymorphisms in the Han population and three other ethnic groups of northeast China.

The allelic distribution of the Y-chromosome specific microsatellite DYS19 in the Han population and in the Daur, Oroqen and Ewenki ethnic groups (Northeast China) was analyzed by PCR and denatured polyacrylamide gel electrophoresis. The allelic distribution in the Han population group is as follows: A = 2.90%, B = 26.09%, C = 26.09%, D = 29.98%, E = 15.94%. This allelic distribution differs statistically significant from that observed in the three other ethnic groups (p < 0.05). Furthermore the polymorphism of the Y-chromosome specific Alu insert sequence DYS287 was tested in these four groups. However, no Alu sequence insert was found.

Alleles↗
PubMed2000

Analysis of polymorphic mitochondrial DNA in the Han population and three other ethnic groups of northeast China.

By means of the PCR-RFLP technique the polymorphism of a 465 fragment of mtDNA D loop was analyzed in 36 individuals of the Northeast Han, 30 individuals of the Daur, 32 individuals of the Oroqen and 30 individuals of the Ewenki. All these individuals were randomly selected and are healthy. 27 restriction patterns were obtained by assaying the RFLP fragments of the mtDNA D loop. The mean nucleid acid substitute frequencies at each site are the following: Northeast Han = 0.0291, Oroqen = 0.0477, Ewenki = 0.0563, Daur = 0.0541. The genetic relationship between these four populations was analyzed by the UPG cluster analysis.

Asian People↗