Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 325 records · Page 18Linked to original sources

PubMed1998

Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold.

OBJECTIVES: We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone's active metabolite desethylamiodarone (DEA). BACKGROUND: Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT. METHODS: We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks. RESULTS: Amiodarone caused a dose-response increase in DFT (mean +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at baseline to 23.1 +/- 7.4 (dose 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p = 0.18. CONCLUSIONS: DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent.

Amiodarone↗

PubMed1998

Translation and psychometric evaluation of a Chinese version of the SF-36 Health Survey in the United States.

Outcome measures are rapidly becoming standard tools in the assessment of clinical effectiveness and in the measurement of health status in populations. In this article we document the development of a self-administered Chinese version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and report the results of psychometric testing among 156 adult Chinese Americans in Boston, Massachusetts. Following the standard guidelines, a Chinese version of the SF-36 was developed through forward-backward translation techniques and committee review. We used psychometric methods to test assumptions underlying construction and scoring of scales and to evaluate the reliability and validity of the Chinese SF-36 as a measure of health status. The preliminary results indicated that missing value rates for the 36 items were consistently low. Item-discriminant validity was high (over 90% scaling successes) for six of the eight scales (Physical Functioning, Role-Physical, Bodily Pain, General Health, Role-Emotional, and Mental Health). Cronbach's alpha coefficient was above 0.70 criterion for all scales except Social Functioning. Reliability estimates also appeared to vary by sample characteristics. We discuss the implications of these findings and identify where further work will be required.

Adult↗

PubMed1998

Synthesis, characterization, and comparative conformational analysis of N-(deoxyguanosin-8-yl)aminopyrene adducts derived from the isomeric carcinogens 1-, 2-, and 4-nitropyrene.

Nitrated polycyclic aromatic hydrocarbons are mutagens/carcinogens that undergo in vivo activation by ring-oxidation and nitro-reduction pathways. We report the syntheses and comparative conformational analyses of N-(deoxyguanosin-8-yl)-n-aminopyrene adducts (dG-C8-n-AP, n = 1, 2, 4) derived from the three isomeric mononitropyrenes (1-, 2-, and 4-NP). The C8-amine nitrogens of these adducts have been enriched with 15N to examine the conformation about the pyrenyl-nitrogen and guanyl-nitrogen bonds that link the guanine and the pyrene moiety. These adducts are structurally isomeric, thus providing an interesting opportunity for systematic probing of the isomeric adduct conformations. Spectroscopic data indicated that the three isomeric aminopyrene adducts favor anti-glycosyl conformations, with C2'-endo (S) sugar puckering and a nearly planar conformation at the central amine nitrogen. The data further indicated differences in the extent of pi-electron conjugations about the pyrenyl-nitrogen bond, depending on the location of aminopyrene substitution. Thus while the 1- and 4-isomers both have substitution adjacent to a fused aromatic ring, the 2-isomer is highly symmetric and less sterically hindered. The 2-isomer adopts the most planar conformation, thereby having the most efficient pi-electron delocalization between the guanine and pyrene rings. The isomeric dG-C8-AP adducts and their nitro and amino precursors display physicochemical properties (HPLC retention time, UV pattern, 1H NMR data, mass fragmentation, etc.) distinctly dependent on their structures (1- and 4-isomers versus 2-isomer).

Carcinogens↗

PubMed1998

Evaluation of in vitro chemosensitivity of antitumor drugs using the MTT assay in fresh human breast cancer.

Practical criteria were developed in this paper for the purpose of evaluating chemosensitivity of fresh human breast cancer by the MTT assay. The survival rates at maximum inhibition (Imax %) and the concentrations of drugs which caused fifty percent reduction in absorbance compared to baseline values (IC50) of 175 samples of 10 anti-tumor drugs were evaluated by logistic analyses of the dose-response curves. Distributions of Imax% appeared as normal curves, while those of the IC50 significantly deviated from normal distribution (p < 0.0001). We assessed the in vitro chemosensitivity by comparing the Imax % of each drug on individual samples with the mean Imax % + SD which was obtained from the Imax% of 175 samples. If the individual Imax % > mean Imax % + SD. we thought the tumor sample was resistant to this drug. If the Imax % < or = mean Imax % + SD, we would compare its IC50 with Q50 which was used as a cutoff point for in vitro chemosensitivity of anti-tumor drugs. The in vitro chemosensitivity could be graded as sensitive (Q1-Q25), intermediate (Q26-Q75), and resistant (Q76-Q100) by means of percentile method. If the individual IC50 > or = Q76, the tumor sample would be defined as resistant. If the individual IC50 < or = Q25, it would be defined as sensitive. In the range of Q26-Q75, we used Q50 as a cutoff point between relative sensitivity and relative resistance. Preliminary results showed that the in vitro chemosensitivity to different anti-tumor drugs determined by these criteria were consistent with the clinical response in 83 advanced breast cancer patients.

Antineoplastic Agents↗

PubMed1998

Distinct cell killing properties of the Drosophila reaper, head involution defective, and grim genes.

The Drosophila reaper, head involution defective (hid), and grim genes play key roles in regulating the activation of programmed cell death. Two useful systems for studying the functions of these genes are the embryonic CNS midline and adult eye. In this study we use the Gal4/UAS targeted gene expression system to demonstrate that unlike reaper or hid, expression of grim alone is sufficient to induce ectopic CNS midline cell death. We also show that in both the midline and eye, grim-induced cell death is not blocked by the Drosophila anti-apoptosis protein Diap2, which does block both reaper- and hid-induced cell death. grim can also function synergistically with reaper or hid to induce higher levels of midline cell death than observed for any of the genes individually. Finally we analyzed the function of a truncated Reaper-C protein which lacks the NH2-terminal 14 amino acids that are conserved between Reaper, Hid, and Grim. Ectopic expression of Reaper-C revealed cell killing activities distinct from full length Reaper, and indicated that the conserved NH2-terminal domain acts in part to modulate Reaper activity.

Animals↗

PubMed1998

Overexpression of Bcl-2 in Kaposi's sarcoma-derived cells.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

Cell Survival↗

PubMed1998

Stimulation of collagen synthesis by the anabolic steroid stanozolol.

There is evidence that anabolic steroids, which are derived from testosterone and have markedly less androgenic activity, promote tissue growth and enhance tissue repair; however, the mechanisms involved in their anabolic activities remain unclear. In this report, we measured the effect of the anabolic steroid stanozolol on cell replication and collagen synthesis in cultures of adult human dermal fibroblasts. Stanozolol (0.625-5 microg per ml) had no effect on fibroblast replication and cell viability (p = 0.764) but enhanced collagen synthesis (p < 0.01) in a dose-dependent manner (r = 0.907). Stanozolol also increased (by 2-fold) the mRNA levels of alpha1 (I) and alpha1 (III) procollagen and, to a similar extent, upregulated transforming growth factor-beta1 (TGF-beta1) mRNA and peptide levels (p < 0.001). There was no stimulation of collagen synthesis by testosterone. The stimulatory effects of stanozolol on collagen synthesis were blocked by a TGF-beta1 anti-sense oligonucleotide, by antibodies to TGF-beta, and in dermal fibroblast cultures derived from TGF-beta1 knockout mice. We conclude that collagen synthesis is increased by the anabolic steroid stanozolol and that, for the most part, this effect is due to TGF-beta1. These findings point to a novel mechanism of action of anabolic steroids.

Adult↗

PubMed1998

Effects of ascorbic acid on levels of fibronectin, laminin and collagen type 1 in bovine trabecular meshwork in organ culture.

PURPOSE: Fibronectin, laminin and collagen type I are important extracellular matrix products of trabecular meshwork cells. This study was performed to examine the effects of ascorbic acid, a significant component in the aqueous humor, on the levels of these proteins in trabecular meshwork cells maintained in organ culture. METHODS: The anterior segment of freshly enucleated bovine eyes was perfused in a modified organ culture system. Three cultures were set up simultaneously. One received serum-free medium containing 100 micrograms/ml of ascorbic acid, one received 250 micrograms/ml of ascorbic acid and one served as a control. After 72 h, the tissues were processed for paraffin sections and immunostaining was conducted using an avidin-biotin-peroxidase complex method. Western blot and dot blot assays were performed on tissue extracts. RESULTS: Compared with the controls, the staining for fibronectin and laminin was markedly enhanced in trabecular meshwork tissues treated with both concentrations of ascorbic acid. Increased collagen type I production by trabecular meshwork cells was also demonstrated in the presence of ascorbic acid. Western blot and dot blot results confirmed the immunostaining findings. CONCLUSIONS: Ascorbic acid promotes production of fibronectin, laminin and collagen type I by trabecular meshwork cells. The organ culture results are consistent with those obtained previously from tissue culture studies.

Animals↗

PubMed1998

A human B cell line AF10 expressing HIL-17.

AF10, a human B cell line, is a mycoplasma-free variant cloned from the human IgE myeloma cell line U266. Total RNA isolated from the AF10 cells was used as template for RT-PCR, and a specific product of about 411bp corresponding to the coding region of hIL-17 lack of a leading sequence obtained. The sequence of the RT-PCR product is the same to that reported in the literature. The expressed rhIL-17 in E. coli can induce 10- to 15-fold increase of IL-6 secretion by mouse fibroblast 3T3 cells. It is for the first time until now that hIL-17 messager has been detected in B cell. There may exist some potential relationship between hIL-17 and myeloma cells.

3T3 Cells↗

PubMed1998

High-level expression of human interleukin-17 in the yeast Pichia pastoris.

Human interleukin-17 (hIL-17) gene without the signal sequence was isolated from activated peripheral blood lymphocytes by RT-PCR, then highly expressed in the yeast Pichia pastoris in the form of the glycosylated monomer. The monomer of rhIL-17 stimulated mouse fibroblast 3T3 cells to secrete IL-6 and was specifically bound to its receptors on 3T3 cells.

3T3 Cells↗

PubMed1998

Age-related changes in type-I collagen synthesis in human eyelid skin.

PURPOSE: This study was to determine whether age-related decrements in type I collagen synthesis occur in human eyelid skin. METHODS: Using an antibody to procollagen I, we investigated collagen synthetic activity in skin removed for cosmetic purposes from 10 white patients between the ages of 4 and 77 years. Eleven masked referees graded the immunostaining on a scale of 1 (most intense) to 10 (least intense). RESULTS: The multiple range test for rank by group demonstrated more intense staining in younger patients compared with older patients. An average correlation coefficient of 0.8432 (p < 0.05) existed between each of the referee's rankings. CONCLUSION: Type I collagen synthesis diminishes with age in eyelid skin.

Adolescent↗

PubMed1998

Cloning, expression in Escherichia coli, and characterization of Arabidopsis thaliana UMP/CMP kinase.

A cDNA encoding the Arabidopsis thaliana uridine 5'-monophosphate (UMP)/cytidine 5'-monophosphate (CMP) kinase was isolated by complementation of a Saccharomyces cerevisiae ura6 mutant. The deduced amino acid sequence of the plant UMP/CMP kinase has 50% identity with other eukaryotic UMP/CMP kinase proteins. The cDNA was subcloned into pGEX-4T-3 and expressed as a glutathione S-transferase fusion protein in Escherichia coli. Following proteolytic digestion, the plant UMP/CMP kinase was purified and analyzed for its structural and kinetic properties. The mass, N-terminal sequence, and total amino acid composition agreed with the sequence and composition predicted from the cDNA sequence. Kinetic analysis revealed that the UMP/CMP kinase preferentially uses ATP (Michaelis constant [Km] = 29 microM when UMP is the other substrate and Km = 292 microM when CMP is the other substrate) as a phosphate donor. However, both UMP (Km = 153 microM) and CMP (Km = 266 microM) were equally acceptable as the phosphate acceptor. The optimal pH for the enzyme is 6.5. P1, P5-di(adenosine-5') pentaphosphate was found to be a competitive inhibitor of both ATP and UMP.

Amino Acid Sequence↗

PubMed1998

Molecular detection of acute lymphoblastic leukaemia in boys with testicular relapse.

AIMS: To determine the role of polymerase chain reaction (PCR) based minimal residual disease (MRD) detection of leukaemia specific DNA in testicular relapse in childhood acute lymphoblastic leukaemia. METHODS: DNA was obtained from archival testicular and bone marrow samples from boys with acute lymphoblastic leukaemia who relapsed in the testes. Overlapping DJH clone specific primers derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each case were used to analyse testicular or bone marrow DNA. RESULTS: Histologically normal end of treatment testicular biopsies in the five patients in longterm remission were all MRD negative, but MRD positive in three of six boys with subsequent testicular relapse. Histologically normal bone marrow samples taken at the end of treatment were MRD negative in five of seven cases, but MRD positive in all cases at the time of isolated testicular relapse. Three boys with unilateral testicular relapse underwent unilateral orchidectomy, rather than bilateral testicular irradiation, as part of their treatment. Two of these boys were MRD positive in the histologically uninvolved testes, and both had subsequent relapses either in the testes or the bone marrow, while the MRD negative patient has not had a testicular relapse. CONCLUSIONS: The presence of MRD in testicular tissue can be assayed with a PCR based method to detect clone specific antigen receptor gene rearrangements. In this setting, PCR is more sensitive than conventional testicular histology for predicting clinical outcomes. MRD assays might be useful in the management of boys at the time of isolated testicular relapse, to confirm the presence of unilateral testicular disease.

Bone Marrow↗

PubMed1998

The effect of minoxidil on keratocyte proliferation in cell culture.

PURPOSE: To determine if minoxidil inhibits keratocyte proliferation in a nontoxic manner. METHODS: Rabbit keratocytes were cultured in Eagle's minimum essential medium supplemented with fetal bovine serum. Minoxidil varying in concentration from 10(0) to 10(3) micrograms/ml was added to the culture medium and incubated for 7 days. The cultures were inspected for morphologic appearance and the cell number was determined at 1, 3 and 7 days after the addition of minoxidil. After 7 days of incubation, minoxidil was withdrawn from the cell culture medium and the cells were examined 3 and 7 days thereafter. In addition, a nonradioactive cytotoxic assay was performed to determine if toxicity is associated with the presence of minoxidil. RESULTS: Minoxidil inhibited keratocyte proliferation in a dose-dependent fashion. 29% of control growth was achieved when keratocytes were cultured for 7 days in 10(3) micrograms/ml, whereas 82% control growth was achieved when keratocytes were cultured in 10(2) micrograms/ml of minoxidil. Intermediate concentrations between 10(2) and 10(3) micrograms/ml produced a linear decline in cell counts in a dose-dependent fashion. The concentration of minoxidil required for 50% control growth at 7 days extrapolated from the dose-response curve was 600 micrograms/ml. Upon withdrawal of minoxidil, cell counts returned to baseline for concentrations of 10(2) micrograms/ml or less. Phase contrast microscopy revealed that the presence of minoxidil was associated with intercellular separation, enlargement of cell bodies and elongated processes. After the withdrawal of minoxidil, the cells in all media reassumed the morphological features of normal keratocytes which included a regular fusiform shape and extensive intercellular contact. The nonradioactive cytotoxic assay revealed the lack of cytotoxicity at all concentrations of minoxidil based on a lack of lactate dehydrogenase release. CONCLUSIONS: Minoxidil inhibits keratocyte proliferation by a nontoxic mechanism. It might be particularly useful for modulating corneal wound healing following excimer laser photorefractive keratectomy.

Animals↗

PubMed1998

Serum angiotensinogen concentration in relation to gonadal hormones, body size, and genotype in growing young people.

Multiple factors are thought to influence the level of circulating angiotensinogen (AGT). We showed previously that the serum AGT concentration was significantly related to body mass index (BMI) in a cohort of young people. In the present study, we studied whether levels of the gonadal hormones estradiol and testosterone might also predict the AGT level and might contribute to the BMI effect, since both the production of these hormones and BMI increase with age. In boys (n=127; mean+/-SD age, 14.7+/-1.9 years) and girls (n=104; age, 14.8+/-1.9 years) studied as a single group, we found a significant association of AGT level with level of estradiol (P=0.015) after adjustment for haplotype, age, race, testosterone concentration, and BMI. In girls studied alone, the level of AGT showed a significantly positive relation to level of testosterone (P=0.043), possibly a result of peripheral conversion of testosterone to estradiol, after adjustment for haplotype, age, race, estradiol concentration, and BMI. In boys, on the other hand, the level of testosterone was inversely related to AGT concentration (P=0.019), again after making adjustments for the other variables. Finally, in pairs of subjects matched for BMI, age, race, and gender where 1 member of each pair had either 1 or 2 copies of an AGT gene haplotype (T235 and -1074t) and the other member had no copy, the level of AGT was higher in the carrier of a haplotype in 24 of the 34 pairs (P<0.001). In conclusion, gonadal hormones are an additional influence on the circulating level of AGT in growing young people. In addition, with matching for BMI and other covariates, there is a strong association of AGT genotype with the serum level of AGT, emphasizing the importance of AGT gene expression as a determinant of the circulating level of AGT.

Adolescent↗

PubMed1998

Effects of hydrolysis of milk glycerides on the antimutagenicity of a hexane extract of milk.

Reconstituted nonfat dry milk was treated with different amounts of lipase from Pseudomonas fluorescens. Hexane extracts of treated milks were dissolved in dimethylsulfoxide and assayed for antimutagenicity using the Ames test (Salmonella typhimurium TA 100) against N-methyl, N'-nitro, N-nitrosoguanidine. Anti-N-methyl, N'-nitro, N-nitrosoguanidine activity increased significantly as the amount of added lipase increased. At the highest lipase concentration tested, activity increased 5-fold, suggesting that liberated fatty acids contributed to the increased antimutagenicity. The activities of mixtures of pure fatty acids on antimutagenesis were examined using the Ames test. At the lowest concentrations tested, mixtures of palmitic and stearic acids and mixtures of palmitic and isopalmitic acids exhibited greater activity than did the individual acids. At all doses tested, mixtures of the monoacylglycerides of palmitic and stearic acids exhibited the same activity as the individual components. Quantification of fatty acids in milk and yogurt by gas chromatography indicated a 2 to 20-fold greater content of free fatty acids in yogurt. The increase in free fatty acids may contribute to the increase in antimutagenicity of yogurt relative to that of milk.

Animals↗

PubMed1998

The carriage of Escherichia coli resistant to antibiotics in healthy populations in Shanghai.

Healthy populations represent the largest reservoir of bacteria resistant to antibiotics. We investigated the resistance of Escherichia coli to 12 antibiotics in fecal samples from untreated healthy populations in Shanghai, China by using Kirby-Bauer (K-B) method. The results showed that: (i) All subjects carried resistant strains of Escherichia coli. (ii) The carriage rates of Escherichia coli resistant to various antibiotics were different, less than 10% to amikacin and 30% to 100% to others. (iii) In the elder children group aged 10-11 years, the percentages of strains resistant to gentamicin, streptomycin, chloramphenicol, tetracycline, trimethoprim, and sulfamethoxazole were significantly lower than those in the younger group aged 5-6 years. In the adult group, the percentages of strains resistant to ampicillin, piperacillin, amikacin, streptomycin, chloramphenicol, tetracycline, trimethoprim, and sulfamethoxazole were significantly lower than those in the elder children group. (iv) The number of strains resistant to five or more antibiotics accounted for 31.8% in the younger children group, 23.7% in the elder children group, and 12.1% in the adult group. These findings suggest that all healthy people in Shanghai carry resistant strains of Escherichia coli in the intestine. The younger the populations, the higher the level of resistance of fecal Escherichia coli to antibiotics. Improvement of health behaviors and environmental sanitation and rational use of antibiotics could remarkedly decrease the resistant level of bacteria.

Adult↗

PubMed1998

Effect of mild hypothermia on the changes of cerebral blood flow, brain blood barrier and neuronal injuries following reperfusion of focal cerebral ischemia in rats.

OBJECTIVE: To compare the effects of mild hypothermia induced in different time courses on rats subjected to 3 hours (h) of ischemia followed by 3 h or 72 h of reperfusion. METHODS: Eighty male Sprague-Dawley rats were divided into three mild hypothermic (MHT, 32 +/- 0.2 degrees C) groups, including intra-ischemia (MHTi), intra-reperfusion (MHTr), and intra-ischemia/reperfusion (MHTi + r) group, and one normothermic group (NT, 37 +/- 0.2 degrees C) as the control. Reversible focal ischemia was carried out in rats with suture model. The cortical blood flow was measured during 3 h of ischemia followed by 3 h of reperfusion. The permeability of brain blood barrier (BBB) was estimated after 3 h of reperfusion. The infarct volume was measured at 72 h after reperfusion to determine the effects of MHT. RESULTS: The acute post-ischemic hyperperfusion and delayed hypoperfusion in ischemic perifocal region and sustained hypoperfusion in ischemic core were inhibited in MHTi + r and MHTi rats (P < 0.05). MHTi + r protection on post-ischemic progressive hypoperfusion in the perifocal region was more effective than that of MHTi (P < 0.05). The BBB disruption and the infarct volume were significantly reduced in both MHTi and MHTi + r groups (P < 0.05), especially in the MHTi + r rats. CONCLUSIONS: This study demonstrates that MHTi + r has more substantial protective effects on reducing ischemia/reperfusion injury than MHTi. It may inhibit post-ischemic hyperperfusion and delayed or sustained hypoperfusion in ischemic perifocal regions, and reduce brain blood barrier disruption in the cortex region.

Animals↗