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Biomedical subjects

Z Huang

Publications and source records attributed to Z Huang.

At least 289 records · Page 16Linked to original sources

[Resection of small primary liver cancer: clinical analysis of 82 cases].

OBJECTIVE: To determine which clinicopathologic features and surgical modalities are related to the prognosis of small primary liver cancer (SPLC). METHOD: Eighty-two patients who had under gone operations for SPLC (<or= 5.0 cm in diameter) from 1988 to 1995 were retrospectively studied. 60 patients were HBsAg positive, and 71 patients suffered from liver cirrhosis. Bisegmentectomy, segmentectomy and partial resections were performed in 13, 14 and 55 patients separately. RESULT: The overall operative mortality was 1.2%, and the 1-, 3-, 5-year survival rates were 92.7%, 72.5% and 54.3%, respectively. The 5-year survival rates of 78 patients with hepatocellular carcinoma according to histologic features were 79.6%, 49.9% and 41.1% in well-differentiated (15 patients), moderately (53), and poorly differentiated (10) groups. Recurrence and metastasis rates in 1, 3, 5 years were 12.8%, 40.7% and 71.5%, separately. CONCLUSION: SPLC has the same history of large PLC. Early diagnosis and limited hepatic resection are very important to decrease the mortality and increase the survival rate.

Adult↗

[The application of solid phase extraction for systematic toxicological analysis of abuse drugs].

A new column was developed in this research. It contains a proprietary bonded silica sorbent that exhibits mixed extraction mechanism. A single-column solid-phase extraction procedure was also developed for the screening of acidic, neutral and basic abuse drugs. The recovery of all 7 tested drugs exceeded 60%. The extraction mechanism for different abuse drugs on the new column was explored and was compared with on other columns. It is suggested that this column be effective in systematic toxicological analysis and better than other columns.

Antipsychotic Agents↗

[Abuse of "pheticol" and its interference to the analysis of methamphetamine].

The study was to eliminate interference from ephedrine in the analysis of methamphetamine. The extraction procedure for methamphetamine was modified to include an oxidation step (2 ml urine specimen was treated with 0.5 ml of 1 mol/L phosphate buffer (pH 6.8) and 0.5 ml 0.3 mol/L sodium periodate). Results showed that ephedrine could be oxidized in the presence of periodate ions into smaller fragments while leaving methamphetamine intact. It is recommended that specimens be treated with sodium periodate prior to extraction in order to eliminate any interference caused by ephedrine.

Central Nervous System Stimulants↗

[Determination of lactitol in mice serum by high performance liquid chromatography].

An HPLC method for the determination of lactitol in mice serum was developed. A liquid chromatograph equipped with a refractive index detector and a Waters Sugar-Pakl column was used. The column temperature was maintained at 90 degrees C and the mobile phase was redistilled water. One milliliter of the serum sample was treated with 3.0 mL methanol. The precipitate was centrifuged for 15 min at 10,000 r/min. Two milliliters of the supernatant was dried on a water bath at 100 degrees C. The residue was dissolved with 1.0 mL water and 10 microL of which was injected. The average recovery was 98.6%. The detection limit was 0.1 microgram (S/N = 3.75). The linear range was 0-600 mg/L (r = 0.9992). Both the RSD's within day and between days were below 1.0% (n = 5).

Animals↗

[Preparation and characterization of monoclonal antibodies against Clonorchis sinensis].

AIM: To develop and identify monoclonal antibody (McAb) against adult Clonorchis sinensis. METHODS: BALB/c mice were immunized with soluble antigen of adult Clonorchis sinensis, the spleen cells of immunized mice were fused with myeloma cell line SP2/0. Then the hybridoma cell lines secreting high titer of McAbs were screened. The Ig subtypes and titer of the McAbs were assayed with ELISA. The antigens recognized by the McAbs were examined with IFAT and identified by immunoblot analysis. The cross reactions between the McAbs and antigens of Schistosoma japonicum, Paragonimus westermani and Cysticercus cellulosae were detected. RESULTS: 5 hybridoma cell lines secreting high titer of McAbs against adult Clonorchis sinensis were established. All five clones of McAbs belonged to IgM subtype. The antigens recognized by the McAbs were located at the intestinal tract wall of adult Clonorchis sinensis. The McAbs had no cross reactions with antigens of Schistosoma japonicum, Paragonimus and Cysticercus cellulosae. CONCLUSION: 5 hybridoma cell lines against adult Clonorchis sinensis secreting high titer of McAbs with high specificity were established.

Animals↗

[In vitro sensitivity of Plasmodium falciparum to chloroquine, piperaquine, pyronaridine and artesunate in Yuxi prefecture of Yunnan province].

AIM: To assess the sensitivity of Plasmodium falciparum to four antimalarials. METHODS: WHO standard in vitro microtest was used. RESULTS: The resistance rates of the malaria parasite to chloroquine, piperaquine pyronaridine and artesunate were 85.7%, 66.7%, 38.1% and 5.0%, respectively. CONCLUSION: Among the antimalarials tested in Yuxi Prefecture, Yunnan Province, high resistance of P. falciparum to chloroquine and piperaquine was found. The sensitivity of P. falciparum in part of the cases to pyronaridine decreased. However, most of the cases were relatively sensitive to artesunate.

Adolescent↗

[Studies on the chemical constituents of soft coral Lemnalia bournei].

The studies on the chemical constituents of soft coral Lemnalia bournei led to the isolation of 2-deoxy-12-oxo-lemnacarnol, 22,23-dihydrobrassicasterol, gorgosterol and batyl alcohol. Their structures were deduced on the comprehensive spectral analysis. The four compounds were first obtained from the soft coral.

Animals↗

Batch fermentation and optimization of media for Bacillus thuringiensis.

The composition of No. II medium obtained with shaking cultivation contained three factors: nitrogen source, carbon source, and inorganic salts. The relationship between component factors (x(i)) of the media and spore numbers (y) of Bacillus thuringiensis (Bt) was demonstrated by the orthogonal-rotation-combination test. A response surface equation was formed as follows: y = 384 - 7.245x1 + 11.705x2 + 15.475x3 + 14.039x1(2) + 41.831x2(2) - 79.49x3(2) - 35.375x1x2 - 3.375x1x3 - 106.625x2x3. The results showed that this method is simple, practical, and rapid enough for selecting fermentation media for Bt. In addition, the whole course of batch fermentation was also investigated.

Bacillus thuringiensis↗

Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2.

Phospholipase A2 (PLA2) enzymes are critical regulators of prostaglandin and leukotriene synthesis and can directly modify the composition of cellular membranes. PLA2 enzymes release fatty acids and lysophospholipids, including the precursor of platelet-activating factor, PAF, from phospholipids. Free fatty acids, eicosanoids, lysophospholipids and PAF are potent regulators of inflammation, reproduction and neurotoxicity. The physiological roles of the various forms of PLA2 are not well defined. The cytosolic form, cPLA2, preferentially releases arachidonic acid from phospholipids and is regulated by changes in intracellular calcium concentration. We have now created 'knockout' (cPLA2-/-) mice that lack this enzyme, in order to evaluate its physiological importance. We find that cPLA2-/- mice develop normally, but that the females produce only small litters in which the pups are usually dead. Stimulated peritoneal macrophages from cPLA2-/- animals did not produce prostaglandin E2 or leukotriene B4 or C4. After transient middle cerebral artery occlusion, cPLA2-/- mice had smaller infarcts and developed less brain oedema and fewer neurological deficits. Thus cPLA2 is important for macrophage production of inflammatory mediators, fertility, and in the pathophysiology of neuronal death after transient focal cerebral ischaemia.

Animals↗

A novel class of peptides that induce apoptosis and abrogate tumorigenesis in vivo.

In testing the ability of certain synthetic peptides of biological origin to bind to cell surfaces, we unexpectedly found that they could induce apoptosis and inhibit tumorigenesis in rodent and human tumor cell lines. In vitro pre-incubation with the peptides at concentrations as low as 10(-12) M inhibited tumorigenesis in nude mice, in a dose-dependent fashion. The inhibition of tumorigenesis was reflected in the rapid induction of apoptosis of tumor cells, pre-incubated with the peptides, and tested under conditions of anchorage-independence. Induction of apoptosis was detectable even at concentrations of 10(-12)-10(-13) M (0.1-1.0 pM). Aspecific toxicity of the synthetic peptides was ruled out by the demonstration that single amino acid substitutions (in at least 4 peptides) completely abrogated the pro-apoptotic effect, even at a concentration of 10(-5) M (10 microM).

Amino Acid Substitution↗

Dual effects of weight and weight gain on breast cancer risk.

CONTEXT: Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease. OBJECTIVE: To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality. DESIGN: Cohort study. SETTING: A cohort of 95256 US female nurses aged 30 to 55 years who were followed up for 16 years. MAIN OUTCOME MEASURE: Incident and fatal breast cancer. RESULTS: During 1203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m2 vs < or = 20 kg/m2; 95% confidence interval, 1.09-2.32; P for trend <.001). Higher BMI at the age of 18 years was associated with lower breast cancer incidence both before and after menopause. Weight gain after the age of 18 years was unrelated to breast cancer incidence before menopause, but was positively associated with incidence after menopause. This increased risk with weight gain was limited to women who never used postmenopausal hormones; among these women, the relative risk was 1.99 (95% confidence interval, 1.43-2.76) for weight gain of more than 20 kg vs unchanged weight (P for trend <.001). Current BMI and weight gain were even more strongly associated with fatal postmenopausal breast cancer. In this population, the percentage of postmenopausal breast cancer accounted for by weight gain alone was approximately 16% and by hormone replacement therapy alone was 5%, but when the interaction between these variables was considered, together they accounted for about one third of postmenopausal breast cancers. CONCLUSIONS: Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones.

Adolescent↗

The reactivity of o-quinones which do not isomerize to quinone methides correlates with alkylcatechol-induced toxicity in human melanoma cells.

Catechols are widespread in the environment, especially as constituents of edible plants. A number of these catechols may undergo oxidative metabolism to electrophilic o-quinones (3,5-cyclohexadien-1,2-dione) by oxidative enzymes such as cytochrome P450 and peroxidases. Alkylation of cellular nucleophiles by these intermediates and the formation of reactive oxygen species, especially through redox cycling of o-quinones, could contribute to the cytotoxic properties of the parent catechols. In contrast, isomerization of the o-quinones to electrophilic quinone methides (4-methylene-2,5-cyclohexadien-1-one, QM) could cause cellular damage primarily through alkylation. In this investigation, we treated human melanoma cells with two groups of catechols. These cells have high levels of tyrosinase required to oxidize catechols to quinoids. For catechols which are oxidized to o-quinones that cannot isomerize to quinone methides or form unstable quinone methides, plots of the cytotoxicity data (ED50) versus the reactivity of the o-quinones gave an excellent linear correlation; decreasing o-quinone reactivity led to a decrease in the cytotoxic potency of the catechol. In contrast, catechols which are metabolized by the o-quinone/p-quinone methide bioactivation pathway were equally cytotoxic but showed no correlation between the reactivity of the o-quinones and the cytotoxic potency of the catechols. The most likely explanation for this effect is a change in cytotoxic mechanism from o-quinone-mediated inhibition of cell growth to a bioactivation pathway based on both o-quinone and p-QM formation. These results substantiate the conclusion that the involvement of the o-quinone/ QM pathway in catechol toxicity depends on a combination between the rate of enzymatic formation of the o-quinone, the rate of isomerization to the more electrophilic QM, and the chemical reactivity of the quinoids.

Biotransformation↗

How does alendronate inhibit protein-tyrosine phosphatases?

Alendronate (4-amino-1-hydroxybutylidene 1,1-bisphosphonate) is a drug used in the treatment of osteoporosis and other bone diseases. The inhibition of protein-tyrosine phosphatases (PTPs) by alendronate suggests that PTPs may be molecular targets. As a clear understanding of the inhibition mechanism is lacking, our aim was to analyze the mechanism to provide further insight into its therapeutic effect. We show here that the inhibition of PTPs by alendronate in the presence of calcium followed first-order kinetic behavior, and kinetic parameters for the process were determined. Evidence is presented that the inhibition by alendronate/calcium is active site-directed. However, this process was very sensitive to assay constituents such as EDTA and dithiothreitol. Furthermore, the inhibition of PTPs by alendronate/calcium was eliminated by the addition of catalase. These observations suggest that a combination of alendronate, metal ions, and hydrogen peroxide is responsible for the inhibition of PTPs. The individual effects of alendronate, calcium, or hydrogen peroxide on the inactivation of CD45 were determined. Electrospray ionization mass spectrometry demonstrated that the mass of PTP1B increased by 34 +/- 2 units after the enzyme was inactivated with alendronate/calcium, due to the oxidization of the catalytic cysteine to sulfinic acid (Cys-SO2H). The inhibited PTP1B could be partially reactivated by treatment with reducing agents such as hydroxylamine (NH2OH) and N,N'-dimethyl-N, N'-bis(mercaptoacetyl)hydrazine, indicating the presence of other oxidized forms such as sulfenic acid (Cys-SOH). This further confirms that the inhibition is the result of oxidation of the catalytic cysteine. The relevance of this oxidative inhibition mechanism in a biological system is discussed.

Alendronate↗

Phosphatidylcholine-fatty acid membranes: effects of headgroup hydration on the phase behaviour and structural parameters of the gel and inverse hexagonal (H(II)) phases.

The phase behaviour and structural parameters of a homologous series of saturated diacyl phosphatidylcholine/fatty acid 1:2 (mol/mol) mixtures having chain lengths from C12 to C20 were studied by X-ray diffraction and calorimetry, as a function of water content. The chain-melting transition temperatures of the 1:2 PC/FA mixtures are found to be largely independent of the degree of hydration. For all chain lengths, the tilted L(beta') and rippled P(beta') gel phases of the pure PC component are replaced by an untilted L(beta) gel phase in the 1:2 PC/FA mixtures. This gel phase swells considerably upon hydration, with a limiting water layer thickness in the range 18-24 A, depending on the chain length. However, unlike pure phospholipid systems, the lateral chain packing within the gel phase bilayers is essentially identical in both the dry and the fully hydrated states. The fluid bilayer L(alpha) phase is suppressed in the 1:2 mixtures, being replaced by inverse non-lamellar phases for all chain lengths greater than C12, and at all levels of hydration. For chain lengths of C16 and greater, the inverse hexagonal H(II) phase is formed directly upon chain melting, at all water contents. For the shorter chain length mixtures, the behaviour is more complex, with the H(II) phase forming at low hydration, but with bicontinuous cubic phases appearing at higher levels of hydration. The implications of these surprising results are explored, in terms of the effective hydrophilicity of the associated PC and FA headgroups and the packing within the interfacial region. We suggest that the presence of the fatty acids significantly alters the lateral stress profile across the lipid monolayer in the fluid state, compared to that of the corresponding pure PC system, such that inverse phases, where the interface bends towards the water, become strongly favoured. Furthermore, for short chain lengths, packing constraints favour the formation of phases with negative interfacial Gaussian curvature, such as the bicontinuous cubic phases, rather than the H(II) phase, which has more severe chain packing frustration.

Calorimetry↗

Alternative splicing of CYP2D mRNA in human breast tissue.

The human cytochrome P450 (CYP) 2D subfamily comprises the CYP2D6 gene and four pseudogenes, CYP2D7P1 and 2 and CYP2D8P1 and 2. The CYP2D6 gene product is a prominent drug-metabolizing enzyme, which is probably constitutive and has no known inducing agents. Alternative splicing of the pre-mRNAs of these genes has been detected in human liver and breast tissue. RNA-PCR, competitive RNA-PCR, Southern blotting, cDNA sequencing, and gene-specific PCR have been used to fully characterize the alternatively spliced forms of CYP2D mRNA in human breast tissue in the region of exon 5 to 8. Such alternative splicing could regulate the expression of CYP2D6 protein. A full-length mRNA (exons 5 to 8), and variants c (exon 6 deleted), b' (3' portion of exon 6 deleted), e (3' portion of exon 6 deleted, 3' 57-bp portion of intron 6 included), d (3' 57-bp portion of intron 6 included), and b (intron 6 included) were characterized and quantitated. Variant c was derived from CYP2D6, variants d, e, and b were from CYP2D7P, and variant b' and full-length mRNA were derived from both CYP2D6 and 2D7P. Full-length mRNA was a minor form in human breast tissue where variants b' and c predominated. Human breast tumor MCF-7 cells had CYP2D mRNA splice variant patterns similar to those of human breast tissue, while human liver tumor HepG2 cells had wild-type mRNA predominating. These results suggest that CYP2D6 could be regulated tissue specifically using tissue-specific alternative mRNA splicing.

Alternative Splicing↗

Comparisons of CYP2D messenger RNA splice variant profiles in human lung tumors and normal tissues.

Allelic variants of the CYP2D6 gene, a member of the cytochrome P450 gene superfamily, have been implicated in susceptibility to lung carcinogenesis. Human breast CYP2D6 and CYP2D7P (from a pseudogene) mRNAs were previously reported to be expressed as a series of splice variants. In this study, the expression of full-length and splice variants of these mRNAs in human lung tissue and tumors are reported for the first time and are compared in order to probe the potential for differential CYP2D6 regulation in lung normal tissue and tumors. The splice variant profiles differed within the same individual, but no consistent differences were detected.

Adult↗

A natural motif approach to protein design: a synthetic leucine zipper peptide mimics the biological function of the platelet factor 4 protein.

The design of smaller functional mimics of large proteins has long been an important challenge. In this study we use the natural leucine zipper as a structural template to design a 31-residue peptide analog that mimics the function of the larger platelet factor 4 (PF4) protein. The heparin binding activity of PF4 has been introduced into an unrelated leucine zipper sequence only by virtue of incorporating four lysines of PF4. Circular dichroism and binding experiments have shown that the designed leucine zipper peptide adopts a stable helical conformation and shows significant PF4-like heparin binding activity. These results strongly suggest that the lysine residues play an important role in the binding of PF4 to heparin. The de novo generation of the PF4 function in a designed leucine zipper peptide demonstrates that the leucine zipper motif is a useful scaffold for the design of functional peptides and proteins.

Amino Acid Sequence↗