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Biomedical subjects

L Zhao

Publications and source records attributed to L Zhao.

At least 379 records · Page 21Linked to original sources

Effects of a 100% perfluorooctylbromide emulsion on ischemia/reperfusion injury following cardioplegia.

Protective effects of a perfluorooctylbromide emulsion on myocardial ischemia and reperfusion (MI/R) injury were evaluated in a modified Langendorff rat heart preparation. Isolated rat hearts were equilibrated in Krebs-Henseleit solution (KH) for 35 minutes and perfused with either cardioplegic solution (CPS) or a 100% perfluorooctylbromide (PFOB) emulsion in CPS for 3 minutes. Hearts were then bathed in the emulsion or CPS. Both groups were subjected to 30 minutes of ischemia. Following 30 minutes of ischemia and 30 minutes of reperfusion with KH solution, hearts subjected to the 100% PFOB emulsion showed improved recovery of left ventricular function. Tissue activities of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase were not affected by the emulsion in this model. Activity of lactate dehydrogenase (LDH) in the bathing medium was elevated at the end of the experimental period in both control and PFOB-treated hearts. The PFOB emulsion reduced the decline in ATP and GSH levels produced by cardioplegia and subsequent reperfusion. No differences were noted in oxidized glutathione (GSSG) levels. These data suggest that the PFOB emulsion provides some protection for the myocardium against injury associated with cardioplegia.

Adenosine Triphosphate↗

[Relationship between serum micronutrients and precancerous gastric lesions].

Serum micronutrient levels and their relationship to precancerous gastric lesions were studied in 600 subjects aged 35-64 years living in high-risk area of gastric cancer in Linqu County, Shandong Province. Serum micronutrient levels in local residents were 0.54 micrograms/ml, 0.29 micrograms/ml, 3.14 micrograms/ml, 9.62 micrograms/ml, 30.2 micrograms/L, 924 micrograms/L, 1 016 micrograms/L, and 42.0 micrograms/L for vitamin A, beta-carotene, vitamin C, vitamin E, selenium, zinc, copper and ferritin, respectively. Serum levels of beta-carotene, vitamin C and ferritin, and ratio of serum levels of zinc and copper correlated inversely to severity of pathological changes in gastric mucous membrane. With increase of serum level of beta-carotene or vitamin C, odds ratios (OR) of intestinal dysplasia and metaplasia lowered to 0.8, 0.6 and 0.9, 0.5, respectively, and with increase of those of both beta-carotene and vitamin C, their OR lowered further to 0.16, with patients of chronically atrophic gastritis as controls. It indicated maybe beta-carotene and vitamin C played a strong contributing role in protecting from development of precancerous gastric lesions.

Adult↗

[In vitro studies on omeprazole metabolism in rat liver microsomes].

The metabolism of omeprazole to its two major metabolites, hydroxyomeprazole (OH-OPZ) and omeprazole sulfone (OPZ-SFN) was studied in rat liver microsomes by a reversed phase HPLC assay. The formation of metabolites of OPZ depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Vmax and Km of OPZ hydroxylation in the rat liver microsomal preparation were 2033 nmol/(min.mg protein) and 46.8 mumol.L-1 respectively. The maximum rate of formation of OPZ-SFN (Vmax) was 187.9 nmol/(min.mg protein), with a Km value of 120.7 mumol.L-1 in rat liver microsome. Moreover, the effects of 7 drugs on OPZ metabolism were tested. The results showed that mephenytoin, benzodiazepines (DZ, NDZ, TMZ, FNZ, NZ) and papaverine caused inhibition of OPZ metabolism, among them papaverine was the only fairly strong inhibitor.

Animals↗

[Affection of growth of zinc deficiency growing rats].

Fifty male Sprague-Dawley rats with an average live mass of 42 +/- 4g were divided into 5 groups of 10 animals each. An artificial semi-systhesis diet was given to the animals. Group 1 received a control diet (32.2 mg Zn/kg DM), and group 2 a zinc deficient diet (3.4 mg Zn/kg DM) ad libitum. The animals of group 3 were pair fed to group 2 with a diet (84.9 mg Zn/KgDM). Diets of group 4 and 5 contained zinc (4.4 and 5.5 kg Zn/micrograms DM), respectively. The two groups also pair fed to group 2. The food intake and live mass gain were observed every day. After 26 days of experiment, the animals were decapitated; the blood samples were collected for the analysis of serum zinc, zinc binding capacity, and alkaline phosphatase.

Animals↗

[Primary lymphomas of bone: a clinicopathologic study of 22 cases].

UNLABELLED: 22 cases of primary lymphoma of bone (PLB) were reported. Multiple bone involvement in two patients, singular bone in twenty patients. One case had regional lymph node involvement. Radiological examination revealed 91% had diffuse lytic lesions. Histological typing was performed according to working formulation. 15 formalin fixed paraffin embedded PLB specimens were studied immunohistochemically by use of the avidin-biotin-peroxide complex (ABC) method to label monoclonal antibodies. RESULTS: Ten neoplasms were B-cell type, there were T-cell type, the two remaining cases did not express. The ratio of primary lymphomas in this study in extranodal lymphomas is three times that reported in Japan and also higher than that reported in north America in recent years. The proportion of T-cell type is also higher than that reported in Japan. Differential diagnosis and several factors which influence immunostaining were also discussed.

Adolescent↗

Analysis of repeated categorical data using generalized estimating equations.

Moment methods for analysing repeated binary responses have been proposed by Liang and Zeger, and extended by Prentice and Zhao and Prentice. In these estimating equations, models are proposed for the correlation between the repeated binary responses. We extend Liang and Zeger's method to models for the correlation between repeated nominal or ordinal categorical responses; in particular, when the repeated responses are binary, our methods reduce to Liang and Zeger's method. Our method is illustrated with two datasets. One dataset contains repeated observations of self-assessment of arthritis, an ordered variable with three categories, collected during a randomized comparative study of alternative treatments of patients with rheumatoid arthritis. The second dataset is a longitudinal study of the health effects of air pollution, in which the repeated ordered multinomial response is the wheezing status (no wheeze, wheeze with cold, wheeze apart from cold) of a child at ages 9, 10, 11 and 12 years.

Adult↗

Differential effect of growth- and differentiation-inducing factors on the release of eicosanoids and phospholipids from ML-1 human myeloblastic leukemia cells.

In the absence of serum, growth of ML-1 human myeloblastic leukemia cells is induced by the insulin-like growth factor-1 (IGF1) together with transferrin (Tf), whereas monocytic differentiation is initiated by the transforming growth factor-beta (TGF-beta) in combination with Tf. Initiation of growth was followed by the rapid release of arachidonic acid (AA), hydroxyeicosatetraenoic acids (HETEs) and phospholipids into the culture medium. In contrast, induction of differentiation occurred without the release of these lipids beyond the level present in control. Inhibitors of enzymes involved in the formation of AA and of HETEs, including phospholipase A2 and lipoxygenases, caused interference with growth but not with differentiation, and an inhibitor of the cyclooxygenase path affected neither growth nor differentiation. These results indicate that the initiation of ML-1 cell growth but not of cell differentiation is dependent upon the increased formation of AA and its derivatives formed primarily via the lipoxygenase path.

Arachidonic Acid↗

Serum micronutrients in relation to pre-cancerous gastric lesions.

Serum levels of retinol, beta-carotene, ascorbic acid, alpha-tocopherol, selenium, ferritin, copper, and zinc were assayed for approximately 600 adults aged 35 to 64 with pre-cancerous gastric lesions in an area of China with one of the world's highest rates of stomach cancer. Previous studies have shown that the cancers generally are preceded by chronic atropic gastritis (CAG), intestinal metaplasia (IM) and dysplasia. Concentrations of beta-carotene and ascorbic acid were significantly lower among individuals with IM than among those whose most severe lesion was superficial gastritis or CAG. The associations with IM for these nutrients were strong and independent. In combination, the odds of CAG progressing to IM were only 1/6 as high among those with upper tertile levels of beta-carotene and ascorbic acid as among those with lower tertile levels of both nutrients. The serum levels of beta-carotene and ascorbic acid were similar for individuals having IM with or without accompanying dysplasia. Risk of IM was also somewhat increased among those with low serum ferritin, but no significant effects were observed in multivariate analyses for the other nutrients assayed. The findings point to a major influence of specific nutrient deficits in the mechanisms of gastric carcinogenesis in this high-risk area.

Adult↗

Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours.

Multiple allelism at loci encoding detoxicating enzymes is associated with cancer risk. We have studied genetic variation at the glutathione S-transferase GSTM1 locus to see whether phenotypes confer altered susceptibility to basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), or multiple skin tumours of different histological types. The frequency of GSTM1 null in cases and controls (52%) was similar, except for patients with two or more tumours of different types (71%, p = 0.033). GSTM1 A/B was reduced in frequency (p < 0.05) in patients with single or multiple BCC. Thus GSTM1 A/B may be protective, and effectiveness of detoxication may be a factor determining susceptibility to skin cancer.

Aged↗

Trisomy 7: a potential cytogenetic marker of human prostate cancer progression.

We used the fluorescence in situ hybridization (FISH) method to show that chromosome 7 trisomy is associated with the progression of human prostate cancer. Thirty-six specimens including 15 primary prostate carcinomas, 16 metastatic lesions, and 5 normal prostate tissues, as well as 2 prostate carcinoma cell lines of different tumorigenic potential, were examined for chromosome 7 aneuploidy. Our results showed that the androgen-unresponsive tumorigenic cell line PC-3 exhibited a significantly higher ratio of chromosome 7 to total chromosome number than the androgen-responsive nontumorigenic cell line LNCaP (P = 0.001). In prostate specimens, the frequency of trisomy 7 cells was significantly increased (P < 0.05) in the advanced stage tumors (C and DI) but not in the early (B) stage tumors or normal prostatic tissue. Furthermore, metastases showed a higher frequency of trisomy 7 cells than primary tumors (P = 0.005). In 2 patients with paired primary and metastatic tumors, trisomy 7 cells increased from 4-7% in the primary tumors to 42-45% in the metastatic tumor cells in the bone marrow. Therefore, our data suggest that trisomy 7 may be a common feature associated with local and metastatic progression and serve as a novel marker for human prostate cancer progression.

Chromosomes, Human, Pair 7↗

5q- chromosome. Evidence for complex interstitial breaks in a case of refractory anemia with excess blasts.

Interstitial loss of the long arm of chromosome 5 (5q-) is an anomaly frequently seen in myelodysplasia (MDS) and acute myelogenous leukemia (AML). Although the limits of the interstitial deletions vary among patients, there is a critical region of overlap at 5q31 that is consistently deleted in most cases. The order of genes in the critical 5q31 region is centromere, interleukin gene cluster, an anonymous polymorphic locus D5S89, early growth response factor, CSF1 receptor, telomere. Fluorescence in situ hybridization of specific 5q31 probes to metaphases with del(5) (q11q31) from a patient with secondary refractory anemia with excess blasts in transformation demonstrates that the interstitial deletion is not contiguous. The 5q- chromosome has lost the D5S89 and CSF1R loci while retaining some of the sequences in between. A probe derived from a 300-kbp yeast artificial chromosome containing the D5S89 locus is interrupted on the normal chromosome 5 of this patient. Data presented in this report are consistent with (i) presence of a critical gene within the YAC and (ii) more than a single interstitial break within the 5q- chromosome. These results, while pinpointing one of the critical 5q31 loci, also provide evidence for a second telomeric locus.

Anemia, Refractory, with Excess of Blasts↗

Effects of alloimmune injury on contraction and relaxation in cultured myocytes and intact cardiac allografts.

OBJECTIVES: This study was performed to determine the mechanisms by which allosensitized lymphocytes cause contractile dysfunction in cultured ventricular myocytes and to compare the effects on isolated myocytes with those observed in an intact heart preparation during allograft rejection. BACKGROUND: Allograft rejection may be associated with reversible abnormalities of both systolic and diastolic function. The immunologic mechanisms that cause ventricular dysfunction are poorly understood. METHODS: Vascularized heterotopic abdominal heart transplantation was performed in mice. Contractile function of excised allografts undergoing rejection was assessed using a Langendorff perfusion apparatus and a strain gauge. Spontaneously beating monolayers of cultured ventricular myocytes from donor strain fetal mice were exposed to the allosensitized cytotoxic T lymphocytes, and the effects on myocyte motion, intracellular calcium transients, relaxation half-time, membrane potential and myocyte lysis (chromium-51 release) were measured. RESULTS: In intact hearts, histologically mild rejection without myocyte necrosis was associated with decreased systolic function without slowing of relaxation. In cultured fetal myocytes, sensitized lymphocytes induced a progressive decrease in the amplitudes of myocyte motion and calcium transients, with cessation of beating within 40 min. Also, the diastolic membrane potential and amplitude of the action potential decreased. Relaxation half-time, as estimated by measurement of cell motion, was unchanged. The effect was allospecific and was reversible with early removal of lymphocytes from the myocyte monolayer. Pretreatment of lymphocytes with the degranulation inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene blocked both the negative inotropic effect and myocyte lysis. CONCLUSIONS: We conclude that impaired relaxation is not a prominent feature of contractile dysfunction caused directly in myocytes by alloimmune injury from cytotoxic lymphocytes. Allosensitized lymphocytes can cause reversible systolic dysfunction in myocytes by means of a direct cell-cell interaction. This effect may be in part responsible for the reversible systolic dysfunction associated with allograft rejection.

Animals↗

A modified product inhibition model describes the nonlinear pharmacokinetics of nicorandil in rats.

Nicorandil, a vasodilator which acts through both cyclic GMP accumulation and K+ channel opening, has been used in the treatment of various cardiovascular diseases. We have examined the pharmacokinetics of nicorandil in the rat as a function of dose, as both i.v. boluses (9 doses, 0.75-12 mg, n = 1.4 per dose), and as a 5-hr infusion followed by a 5-hr washout (6 doses, 10-500 micrograms/kg/min, n = 3 per dose). Plasma nicorandil concentrations were determined by HPLC. Nicorandil plasma concentrations increased disproportionately with dose, but nicorandil elimination obeyed apparent monoexponential kinetics, and the apparent half-life (t1/2) increased with dose. In addition, the approach to apparent steady-state during the infusion phase was not overtly sensitive to the drastic changes in t1/2 observed. Pharmacokinetic modelling with several nonlinear models, viz: Michaelis-Menten with parallel first-order, cosubstrate depletion and competitive product inhibition, were carried out. Addition of the sulfhydryl donor, N-acetyl-L-cysteine, did not change the pharmacokinetics of nicorandil, providing experimental indication that a cosubstrate depletion model might not be applicable. To described the unique pharmacokinetics, a modified product inhibition model was developed. This new model includes the classic competitive product inhibition equation, describing both parent and product kinetics, and it incorporates, in addition, separate first-order elimination rate constants for both nicorandil and the inhibition metabolite. Experimental evidence showed that N-(2-hydroxyethyl) nicotinamide, the major metabolite of nicorandil in rats, and nicotinamide (niacinamide) itself, indeed inhibited nicorandil elimination.

Animals↗

Reversal of pulmonary vascular remodelling following hypoxic exposure: no effect of infusion of atrial natriuretic factor and neutral endopeptidase inhibitor.

OBJECTIVE: The aim was to investigate whether infusion of either atrial natriuretic factor (ANF, 800 ng.h-1.rat-1) or a specific inhibitory of neutral endopeptidase 24.11 (NEI, UK 73,967, 5.4 mg.kg-1.d-1) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia. METHODS: Male Wistar rats were kept in a normobaric hypoxic chamber (FiO2 = 10%) for 7 d. Chronically hypoxic rats were then treated with intravenous infusion of vehicle, ANF, or NEI by osmotic minipumps. Measurements of pulmonary artery pressure, systemic blood pressure, heart rate, right ventricular hypertrophy, micro-haematocrit, and pulmonary vascular remodelling (percentage of thick walled peripheral vessels) were made in all the rats at different time points. RESULTS: The changes in packed cell volume, right ventricular hypertrophy, and pulmonary hypertension induced by a 7 d hypoxic exposure diminished gradually and returned to normal at different time points during the 24 d recovery period. In contrast, vascular hypertrophy in peripheral pulmonary arteries was present after 24 d. There were no significant differences in pulmonary arterial pressure, packed cell volume, right ventricular hypertrophy and vascular remodelling between ANF, NEI, and vehicle treatment groups at either day 8 or day 15. CONCLUSIONS: ANF and NEI treatment had no effect on the reversal of pulmonary hypertension, right ventricular hypertrophy, and vascular remodelling, in contrast to the beneficial actions of ANF and NEI during the development of pulmonary vascular remodelling.

Animals↗

The relationship of dietary animal protein and electrolytes to blood pressure: a study on three Chinese populations.

The relationship of diet to blood pressure was studied in a total of 705 men and women aged 40-59 from three Chinese population samples having different mean blood pressure and dietary sodium and animal protein intake. Two groups were farmers from Shanxi in northern China, and Guangxi in southern China, and the third were fishermen from Zhejiang, eastern China. Three 24-hour dietary recalls were done for each participant. Serum and overnight urine amino acids were measured in random subsamples. Determination of electrolytes in three 24-hour urine specimens was done in an additional sample of 59 men in each population. Results of multiple or stepwise regression showed: 1) in the pooled group, individual intake of sodium was positively associated with systolic blood pressure; 2) when stratifying by median calcium intake, a positive association of dietary sodium or sodium/potassium was found only in the group with calcium intake lower than the median; 3) daily intake of animal protein, urinary sulphate and certain serum and urine amino acids formed from protein metabolism, were inversely associated with blood pressure.

Adult↗