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Biomedical subjects

M Zhou

Publications and source records attributed to M Zhou.

At least 253 records · Page 14Linked to original sources
PubMed1996

Thermodynamic studies of SHC phosphotyrosine interaction domain recognition of the NPXpY motif.

The N-terminal 200 amino acids of SHC constitute a unique phosphotyrosine (Tyr(P)) interaction (PI) domain that shows no significant sequence similarity to the other Tyr(P)-recognizing module, the SH2 domain. We describe the thermodynamic parameters characterizing PI domain binding to various tyrosyl phosphopeptides, using isothermal titration calorimetry. The PI domain forms 1:1 complexes of similar affinity with a 12-mer peptide (ISLDNPDpYQQDF) derived from Tyr-1148 of the epidermal growth factor receptor (EGFR) (KD = 28 nm) and an 18-mer (LQGHIIENPQpYFSDACVH) derived from Tyr-490 of Trk (KD = 42 nM). Binding of the EGFR-derived peptide was largely enthalpy-driven at 25 degrees C, while Trk490 peptide binding was entropy-driven. Based on the change in heat capacity upon binding, approximately 700 A2 of nonpolar surface was estimated to be buried upon interaction. Alteration of the Asn or Pro to Ala in the NPXpY motif of the EGFR Tyr-1148 peptide increased the KD of PI domain interactions to 238 and 370 nM, respectively. Alteration of a Leu at position -5 (with respect to Tyr(P)) in the EGFR peptide to Gly also reduced the binding affinity (KD = 580 nM). It is proposed that the PI domain recognizes the beta1 turn that is found in NPXpY-containing peptides and also interacts with a larger segment of the peptide than seen for SH2 domains.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Concentration of rare earth elements, As, and Th in human brain and brain tumors, determined by neutron activation analysis.

Toxic elements As and Th, six rare-earth elemental profiles of brain tumor tissues from 16 patients of astrocytomas (grade I-III), and normal human brain tissues of 18 male, age-matched autopsies serving as controls have been studied by radiochemical neutron activation analysis. P-204 [di(2-ethylhexyl) phosphate] extraction chromatography column was used for group separation of rare-earth element (REE) by one step. Compared with the normal brain tissues, the analytical results showed that the concentrations of Th, La, Ce, Gd, and Lu were significantly higher in tumor tissues (P < 0.01 or 0.001). The possible effects of REE on tumor cell were discussed.

Adult↗
PubMed1996

Lipoperoxidative injury to macrophages by oxidatively modified low density lipoprotein may play an important role in foam cell formation.

Both oxidatively and malondialdehyde modified low density lipoprotein (Ox-LDL and MDA-LDL) could be recognized by the scavenger receptor and induce intracellular cholesteryl ester accumulation of macrophage. The cholesteryl ester accumulation caused by MDA-LDL could be largely cleared by high density lipoprotein (HDL3), but that caused by Ox-LDL could not be. Further studies showed that Ox-LDL and MDA-LDL all could decrease the binding capacity of HDL3 and increase intracellular thiobarbituric acid reactive substances (TBARS). When macrophages were first cultured with MDA-LDL and then in medium without LDL, the decreased binding capacity of HDL3 was somewhat recovered and the intracellular TBARS did not increase any more. However, if macrophages were first cultured with Ox-LDL, the binding capacity of H DL3 continued to decrease and intracellular TBARS continued to increase. There was a negative correlation (r = -0.81, P < 0.01) between the decreased binding capacity of HDL3 and the increased intracellular TBARS caused by Ox-LDL. These results imply that lipid peroxidative injury to macrophages caused by Ox-LDL play an important role in foam cell formation.

Animals↗
PubMed1996

Mineralocorticoids, salt and high blood pressure.

Essential hypertensive patients often respond to treatments mitigating mineralocorticoid action, even though circulating levels of these steroids are within normal ranges. In addition to the kidney, mineralocorticoid or Type I receptors are found in the brain and vascular smooth muscle where they mediate effects associated with several forms of experimental hypertension. Studies in which discrete anatomic or functional areas of the brain have been ablated demonstrate that the periventricular areas of the hypothalamus and the central sympathetic and baroreceptor systems are crucial for the development of hypertension in the renoprival, DOCA salt, and Dahl salt-sensitive rat. Intracerebroventricular (i.c.v.) infusion of aldosterone in both rats and dogs at doses that do not raise serum levels above normal produce hypertension. The hypertension produced by systemic mineralocorticoid excess, adrenal regeneration, and i.c.v. or oral administration of glycyrrhetinic acid or carbenoxolone in genetically normotensive rats and by dietary salt in the Dahl salt-sensitive rat is inhibited by the i.c.v. infusion of a mineralocorticoid receptor antagonist or a Na+ channel-selective amiloride analog. Recent data demonstrate the extraadrenal synthesis of steroids in aortic endothelial cells, smooth muscle cells and the brain. The role of the extraadrenal synthesis of steroids raises new avenues for research into the causes of hypertension.

Adrenal Cortex Hormones↗
PubMed1996

A nomogram to predict the best biological half-life values for candidates for oral prolonged-release formulations.

It is sometimes possible to maintain plasma concentrations between desired maximum and minimum limits by repetitively administering a drug in an oral prolonged-release formulation when this goal cannot be achieved with a rapid-release formulation. However, this approach does not work with all drugs. The biological half-life value of the drug can be one cause for failure of this approach. Although it is recognized that a half-life may be too long or too short, neither the criteria for determining these values nor the consequences of failing to meet them have been established. The best half-life values for prolonged-release candidates were found by simulating once-a-day and twice-a-day administration of formulations and examining the capacity of these formulations to maintain steady-state plasma concentrations between various selected limits. These observations were used to establish criteria to judge the acceptability of half-lives. Half-life values were considered too long if drugs were self-sustaining and simulations of their rapid-release formulations were also successful. Half-life values were considered too short if minor variability in prolonged-release rates resulted in plasma concentrations above and/or below the selected limits. The actual half-life values that were considered too long or too short depended on the dosing interval and the selected maximum and minimum plasma concentrations. A nomogram was constructed to assess the acceptability of the biological half-life of a candidate for once-a-day or twice-a-day prolonged-release formulations. The nomogram employs the user-selected limits for the desired plasma concentrations to predict whether the half-life of a candidate is (1) too long, (2) too short, or (3) acceptable (i.e., between 1 and 2).

Administration, Oral↗
PubMed1996

Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo.

The influence of microenvironment on the course of CD8 + T cell responses in vivo was investigated by injecting H-2Kb-specific T cells from donor TCR transgenic (TCR-Tg) mice into H-2kb-Tg mice. H-2Kb expression in recipients was either ubiquitous (CBK mice) or restricted to myeloid and erythroid cells (K beta mice). Donor T cells proliferated as extensively and acquired similar surface phenotypes in spleen of both recipient types. Thus, neither the restricted pattern of H-2Kb expression nor the significantly reduced level of H-2Kb expression by myeloid cells in Kbeta recipients affects the ability of the splenic microenvironment to prime T cell proliferation in vivo. However, an unsustained burst of cytolytic activity was generated rapidly in spleen of CBK recipients, whereas relatively little cytolytic activity was generated in K beta spleen. This indicates that effector T cells were not generated efficiently in spleen of Kbeta recipients even though extensive T cell proliferation was taking place in this microenvironment. Furthermore, activated donor T cells dispersed rapidly throughout primary and secondary lymphoid organs of Kbeta recipients, whereas few T cells migrated from spleen in CBK recipients. Consequently, the course of CD8+ T cell responses and the anatomical distribution of activated T cells are profoundly influenced by the nature of the antigenic microenvironment encountered in vivo. We conclude that T cells rapidly proliferate and acquire new tissue-homing characteristics but do not differentiate into cytolytic effector cells at the site of priming when they encounter myeloid cells expressing low levels of antigen in vivo.

Animals↗
PubMed1996

Inhibition of the biologic activity of tumor necrosis factor maintains vascular endothelial cell function during hyperdynamic sepsis.

BACKGROUND AND OBJECTIVE: Although vascular endothelial cell function (i.e., the release of endothelium-derived nitric oxide) decreases and plasma tumor necrosis factor (TNF) increases during sepsis, it is not known whether the elevated TNF is responsible for the depression of endothelial cell function under such conditions. The aim of this study, therefore, was to determine if inhibition of TNF biologic activity by polyethylene glycol dimerized conjugate of the recombinant human form of the p55 soluble TNF receptor (PEG-(rsTNF-R1)2) maintains endothelial function during sepsis. DESIGN, MATERIALS AND METHODS: Rats were subjected to sepsis by cecal ligation and puncture (CLP). Immediately before the onset of sepsis, 600 microgram/rat PEG-(rsTNF-R1)2 or an equal volume of saline was infused intravenously. At 10 hours after CLP (i.e., hyperdynamic sepsis), the thoracic aorta was isolated, cut into rings, and placed in organ chambers. Dose responses for an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerine (NTG), were determined. Endothelial cell structure was examined by transmission electron microscopy. RESULTS: Endothelium-dependent vascular relaxation was depressed at 10 hours after the onset of sepsis. Administration of PEG-(rsTNF-R1)2 before CLP, however, maintained ACh-induced relaxation. In contrast, no significant difference in NTG-induced relaxation was seen, irrespective of administration of PEG-(rsTNF-R1)2 Furthermore, the deterioration in endothelial structure during sepsis was prevented by PEG-(rsTNF-R1)2 pretreatment. CONCLUSION: Since administration of PEG-(rsTNF-R1)2 maintains vascular endothelial cell structure and function, it can be concluded that TNF plays a pivotal role in producing endothelial dysfunction during sepsis. Thus, pharmacologic agents that inhibit TNF biologic activity and/or its production may be useful for protecting endothelial cells during sepsis.

Acetylcholine↗
PubMed1996

Sequence variation in the 18S rRNA gene, a target for PCR-based malaria diagnosis, in Plasmodium ovale from southern Vietnam.

Field surveys of malaria were performed in southern Vietnam by using an acridine orange staining method for rapid diagnosis and a PCR-based, microtiter plate hybridization method for accurate diagnosis. A total of three patients of Plasmodium ovale infection were detected, but PCR-amplified DNA of the P. ovale isolates from two of the patients did not hybridize with the P. ovale-specific probe. Analysis of the target sequence in the 18S rRNA gene indicated that in the DNA of isolates from both patients three nucleotides in the probe region from the typical P. ovale sequence were different, with deletions of two nucleotides and the substitution of one nucleotide. These results may suggest that in addition to molecular biological methods, careful microscopic examination of stained thin blood films is still required in studies of the prevalence of different malaria species.

Animals↗
PubMed1996

Effects of nonanticoagulant heparin on cardiovascular and hepatocellular function after hemorrhagic shock.

Although heparinization of animals before hemorrhage improves cell and organ function, the potent anticoagulant activity of conventional heparin sodium precludes its potential clinical use. To determine whether a novel nonanticoagulant heparin, GM1892, would have any beneficial effects on cardiovascular and hapatocellular functions and would decrease susceptibility to sepsis after hemorrhage, laparotomy was performed on rats (i.e., trauma induced), after which they were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleedout volume was returned in the form of Ringer lactate solution (RL). The rats were then resuscitated with three times the volume of shed blood with RL over 45 min, followed by infusion of two times RL plus GM1892 (7 mg/kg body wt; approximately 2% the anticoagulant activity of regular heparin) of saline over 60 min. At 2 and 4 h after the completion of resuscitation, cardiac output, hepatocellular function, and microvascular blood flow were determined. The results indicated that cardiac output, hepatocellular function, and microvascular blood flow in the liver, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Administration of GM1892, however, restored these parameters. The morphological abnormality observed after hemorrhage in the liver, kidney, and small gut was also attenuated with GM1892 treatment. Moreover, GM1892 normalized the elevated plasma prostaglandin E2 levels. Sepsis was induced in additional rats by cecal ligation and puncture (CLP) 20 h after hemorrhage, and the necrotic cecum was excised 10 h thereafter. GM1892 treatment significantly decreased mortality after CLP and cecal excision. Thus GM1892 appears to be a useful adjunct to fluid resuscitation, since it restores the depressed cardiovascular responses and decreases susceptibility to sepsis after trauma and hemorrhage.

Animals↗
PubMed1996

11 beta-Hydroxysteroid dehydrogenase type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11 alpha-hydroxyprogesterone.

The 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD-2) enzyme is thought to confer aldosterone specificity upon mineralocorticoid target tissues by protecting the mineralocorticoid receptor from binding by the more abundant glucocorticoids, corticosterone and cortisol. We have developed a Chinese hamster ovary cell line stably transfected with a plasmid containing the rat 11 beta HSD-2 complementary DNA. This cell line has expressed the enzyme consistently for many generations. The 11 beta HSD-2 was located primarily in the microsomes, but significant amounts also existed in the nuclei and mitochondria. The enzymatic reaction was unidirectional, oxidative, and inhibited by the product, 11-dehydrocorticosterone, with an IC50 of approximately 200 nM. The K(m) for corticosterone was 9.6 +/- 3.1 nM, and that for NAD+ was approximately 8 microM. The enzyme did not convert dexamethasone to 11-dehydrodexamethasone. Tunicamycin, an N-glycosylation inhibitor, had no effect on enzyme activity. 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM). 11 beta OH-P, progesterone, and GA were almost equipotent (IC50 = 10 and 6 nM, respectively), and 5 alpha-pregnandione and 5 beta-pregnandione were less potent (IC50 = 100 and 500 nM, respectively) inhibitors of the enzyme. When the inhibitory activities were examined with intact transfected cells, 11 alpha OH-P was more potent than GA (IC50 = 5 and 150 nM, respectively). 11 alpha OH-P was not metabolized by 11 beta HSD-2. We were unable to demonstrate the presence of 11 alpha OH-P in human urine. In conclusion, a cell line stably transfected with the rat 11 beta HSD-2 was created, and the enzyme kinetics, including inhibition, were characterized. 11 alpha OH-P was found to be a potent relatively specific inhibitor of the 11 beta HSD-2 enzyme. Its potential importance is that it is the most specific inhibitor of the 11 beta HSD-2 so far encountered and would aid in the study of the physiological importance of the isoenzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

[Anti-embryonation immunity and cultivation of Schistosoma japonicum eggs in vitro].

OBJECTIVE: To study anti-SIEA super-immune sera against the influence on schistosoma japonicum in vitro cultivation of newly laid eggs by adult worms, their hatches and development. METHODS: The adult worm pairs of Schistosoma japonicum were collected from test animals, portae vena which infected with the worms for 38-45 days. The worm pairs were injected divided into control group with normal rabbit sera and experimental group with anti-SIEA super-immune sera. The output of newly laid eggs and the embryonic development were observed with immunofluorescence staining. RESULTS: Female worms cultured in vitro with normal rabbit serum not only discharged eggs already contained in its uterus, but also produced newly formed ones. They however, did not occur in female worms cultured with anti-SIEA super-immune sera and the output of eggs by the latter was much lower than that of the former. There was also a marked decrease in the proportion of developed eggs in the experimental group compared with that in the control group. In addition, immunofluorescence staining of immature eggs and female worms by anti-SIEA super-immune sera showed that a lightened fluorescence was not only seen in the embryonic cells of immature eggs, but also in the vitelaria and in the internal membrane tissue of gut cavity of the female worms. CONCLUSION: SIEA was possibly involved in the immunity against egg development and fecundity of schistosoma japonicum.

Animals↗
PubMed1996

[Using a lipid clearing drug to prevent osteocytes damage of the femoral head in steroid-treated rabbits].

OBJECTIVE: We investigated experimentally the prevention of steroid-induced osteonecrosis of the femoral head. METHODS: Twenty-three rabbits were divided into three groups: (Group S) steroid treated, (Group T), steroid and clofibrate treated, and controls. Serological tests (cholesterol and triglyceride), histology and histochemical studies and electron microscopic examination were performed six weeks after treatment. RESULTS: The serum cholesterol and TG levels increased obviously in Group S. Although Group T animals also showed hyperlipidemia, their serum cholesterol and TG levels were much lower than those for Group S. Group S animals demonstrated fatty degeneration of the liver. Lipid droplets were seen in the osteocytes of the femoral heads of these animals, which compressed the nucleus of the osteocytes along with nuclear pyknosis or absent nuclei. However, the construction of liver cells and osteocytes of the femoral head were almost normal in Group T. Lipid containing osteocytes were not seen in these animals. CONCLUSION: These observations demonstrated that clofibrate decreased hyperlipidaemia, modified lipid metabolism, and diminished steroid-induced damage to the osteocytes. This finding may be a guide to protect against steroid-induced osteonecrosis of the femoral head.

Animals↗
PubMed1996

Analysis of Chinese isolates of Trichinella spiralis by molecular biotechnology.

OBJECTIVE: To investigate the relationships among Trichinella spiralis isolates obtained from different hosts and geographical regions in China. MATERIALS AND METHODS: Six isolates of Trichinella spiralis obtained from Changchun, Tianjin, Xi'an, Henan and Yunnan were detected. All the isolates were collected from pigs or dogs. Restriction fragment length polymorphism (RFLP), isoenzyme electrophoresis and soluble protein analysis were used. RESULTS: Distinctive banding patterns in restriction maps were seen between Changchun and other isolates studied. A cloned specific repetitive DNA sequence (1.12 kb) from Changchun isolate was then selected to prepare probe for Southern blotting of DNA fragments. The hybridizing banding patterns among the isolates were different and only the Changchun isolate showed the 1.12 kb band. The Changchun isolate was also distinguishable from the other isolates in isoenzyme patterns of GP1, G6PD, HK, 6PGDH and AK, as well as in isoelectric focusing electrophoresis where the Changchun isolate presented a specific band at 4.1 P1. CONCLUSIONS: There are at least two different biological types of Trichinella spiralis in China and the differences between them may be attributed to different geographical origins and/or different hosts.

Animals↗
PubMed1996

Endoscopic Intranasal dacryocystorhinostomy in forty-five patients.

OBJECTIVE: To observe the results of endoscopic intranasal dacryocystorhinostomy. METHODS: Forty-five patients (forty-eight eyes) suffering from chronic dacryocystitis received endoscopic intranasal dacryocystorhinostomy after November 1991, and were followed up for 3 to 36 months. RESULTS: Thirty-nine eyes were cured (81.2%). It is significantly effective (8.3%) in 4 eyes, and effective in 2 eyes (4.2%). The total effective rate was 93.7%. CONCLUSIONS: The intranasal approach is simple causing little bleeding and no facial scar. With the self-made dacryocyst-illuminator (diameter = 0.8 mm), and by transilluminating the lacrimal sac with fiberoptic intraocular endoilluminator bundle, the sac can be located endonasally, thus facilitating the approach.

Adult↗
PubMed1996

[The significance of detecting Epstein-Barr virus DNA and latent membrane protein I in Hodgkin's disease from a high incidence area of nasopharyngeal carcinoma].

To study the EBV DNA and expression of latent membrane protein I (LMP1) in patients with Hodgkin's disease from high incidence area of nasopharyngeal carcinoma, hot starting PCR and microwave treatment of LSAB immunohistochemistry methods were used to detect EBV DNA and LMP1 from biopsy specimens from 40 cases of Hodgkin's disease (HD) and 20 cases having benign lymph node lesions, randomly selected from a high incidence area of nasopharyngeal carcinoma. EBV DNA was detected in 65.0% of the HD cases and 50.0% of the benign lymph node cases, the difference was not of statistical significance. LMP1 of EBV was detected in 52.5% of HD cases and its expression was restricted to tumor cells. In addition, the detection rates of LMP1 and DNA of EBV in patients under 20 years of age (84.6% and 76.9% respectively) was much higher than that in patients over 20 years of age (56.0% and 40.0% respectively) P < 0.05. The results suggest that there was latent EBV infection in at least half of HD patients, which may have a role in the genesis and development of HD, and HD occurring in youth was more closely correlated with EBV latent infection and LMP1 expression.

DNA, Viral↗