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Biomedical subjects

Z Zhou

Publications and source records attributed to Z Zhou.

At least 361 records · Page 20Linked to original sources
PubMed1997

[Preliminary evaluation on bone mass of tibia by ultrasonic measurement].

The speed of ultrasound (SOS) in right middle tibia and bone mineral density (BMD) of left radius at the distal one-third were measured by ultrasonic measurement and single photoabsorptionmetry in 260 healthy individuals simultaneously. SOS of tibia was positively correlated with BMD of radius (r = 0.64). The peak bone mass of both measurements was at 33 to 36 years of age. Height was positively correlated with the SOS of tibia, while weight was positively correlated with SOS of female tibia, period of menopause negatively correlated with female's SOS of tibia. The concordance of SOS of tibia and BMD of radius in diagnosis of osteoporosis was 36.8%. The results suggest that ultrasonic measurement of tibia is an effective method of bone mass measurement.

Adolescent↗
PubMed1996

The cumulative electrostatic effect of aromatic stacking interactions and the negative electrostatic environment of the flavin mononucleotide binding site is a major determinant of the reduction potential for the flavodoxin from Desulfovibrio vulgaris [Hildenborough].

Flavodoxins are typified by the very low one-electron reduction potential for the semiquinone/hydroquinone couple (Esq/hq) of the flavin mononucleotide (FMN) cofactor. In the Desulfovibrio vulgaris flavodoxin, the elimination of the side chain of Tyr98, which flanks the outer or si face of the flavin, through the Y98A mutation results in a substantial increase in Esq/hq of 139 mV, representing about one-half of the total shift in Esq/hq in this flavodoxin [Swenson, R. P., & Krey, G. D. (1994) Biochemistry 33, 8505-8514]. The extent to which this large effect was the result of the elimination of unfavorable coplanar aromatic stacking interactions or to the greater solvent exposure of the flavin ring was not known. The significance of the latter effect was heightened by the characterization of the Fld+6 mutant which demonstrated that the unfavorable interaction between the negative electrostatic environment provided by the asymmetric clustering of acidic residues surrounding the cofactor and the FMN hydroquinone anion is responsible for about one-third of the total decrease in Esq/hq in this flavodoxin [Zhou, Z., & Swenson, R. P. (1995) Biochemistry 34, 3183-3192]. In this study, a flavodoxin mutant was generated in which an alanine was substituted for Tyr98 while at the same time the negative electrostatic surface was partially neutralized by the substitution of the six acidic amino acid residues with their amide equivalents. The Esq/hq value of this mutant was found to have increased by 221 mV relative to wild type, which accounts for 70-80% of the total shift in Esq/hq in this flavodoxin. This increase is very similar to the sum of the individual changes in Esq/hq introduced independently in the Y98A and Fld+6 mutants. The similarity in the magnitude of the effect of the neutralization of the six acidic residues in the context of an alanine residue at position 98 (Y98A) relative to an aromatic tyrosine residue (wild type) suggests that the increase in Esq/hq observed for the Y98A mutant is more likely due to the elimination of unfavorable pi-pi interactions between Tyr98 and the FMN hydroquinone rather than to the increased solvent exposure of the flavin. This study provides further support for the concept that the cumulative effect of the unfavorable electrostatic interactions introduced by coplanar aromatic or pi-pi stacking interactions and the negative electrostatic environment of the FMN binding site is a major determinant of the low one-electron reduction potential of the flavodoxin.

Binding Sites↗
PubMed1996

Torsade de pointes with an antihistamine metabolite: potassium channel blockade with desmethylastemizole.

OBJECTIVES: Proarrhythmic effects have been observed with the selective histamine1 (H1) receptor antagonist drug astemizole, a widely prescribed antihistamine. The metabolites of astemizole and those of other antihistamine compounds have not been implicated as causative agents of cardiac arrhythmias. The purpose of this study was to examine whether desmethylastemizole, the principal metabolite of astemizole, blocks delayed rectifier potassium (K+) channels. BACKGROUND: QT interval prolongation and torsade de pointes are associated with astemizole intake and have been ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. Astemizole undergoes extensive first-pass metabolism, and its dominant metabolite, desmethylastemizole, has a markedly prolonged elimination time. We report the clinical observation of QT prolongation and torsade de pointes in a patient with undetectable serum concentrations of astemizole (< 0.5 ng/ml) and "therapeutic" concentrations of desmethylastemizole (up to 7.7 ng/ml or 17.3 nmol/liter). METHODS: The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes. RESULTS: Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations. Under voltage clamp conditions, desmethylastemizole suppressed iKr amplitude by approximately 65%. The drug E-4031 (100 nmol/liter), which selectively blocks iKr, had a similar effect on current amplitude. CONCLUSIONS: Desmethylastemizole, the major astemizole metabolite, blocks the repolarizing K+ current iKr with high affinity. The clinical observation of QT prolongation and torsade de pointes found with astemizole intake may principally be caused by the proarrhythmic effects of its metabolite desmethylastemizole.

Aged↗
PubMed1996

Early Adaptive Radiation of Birds: Evidence from Fossils from Northeastern China

Late Jurassic and Early Cretaceous birds from northeastern China, including many complete skeletons of Confuciusornis, provide evidence for a fundamental dichotomy in the class Aves that may antedate the temporal occurrence of the Late Jurassic Archaeopteryx. The abundance of Confuciusornis may provide evidence of avian social behavior. Jurassic skeletal remains of an ornithurine bird lend further support to the idea of an early separation of the line that gave rise to modern birds. Chaoyangia, an ornithurine bird from the Early Cretaceous of China, has premaxillary teeth.

Journal Article↗
PubMed1996

Evaluation of the electrostatic effect of the 5'-phosphate of the flavin mononucleotide cofactor on the oxidation--reduction potentials of the flavodoxin from desulfovibrio vulgaris (Hildenborough).

Two mutants of the Desulfovibrio vulgaris flavodoxin, T12H and N14H, were generated which, for the first time, place a basic residue within the normally neutral 5'-phosphate binding loop of the flavin mononucleotide cofactor binding site found in all flavodoxins. These histidine residues were designed to form an ion pair with the dianionic 5'-phosphate, either altering its ionization state or offsetting its negative charge to allow evaluation of the magnitude of its electrostatic effect on the redox properties of the cofactor. The midpoint potential for the oxidized/semiquinone couple was not significantly altered in either mutant. However, the midpoint potentials for the semiquinone/hydroquinone couple (Esq/hq) were less negative than that of the wild type, increasing by 28 and 15 mV relative to that of the wild type for the T12H and N14H mutants, respectively, at pH 6. 31P NMR spectroscopy suggests that, just as for wild type, the phosphate group in each mutant does not change its ionization state between pH 6 and 8. Therefore, the small increases in midpoint potential must be linked to the protonation of the histidine residues, either through favorable interactions with the anionic hydroquinone or by the partial compensation of the charge on the 5'-phosphate. Values for the pKa of His12 and His14 in the oxidized flavodoxin were determined by 1H NMR spectroscopy to be 6.71 and 6.93, respectively, which are only modestly elevated relative to the average value for histidines in proteins. This suggests that the histidines do not form strong ion-pairing interactions with the phosphate and/or that the effective charge on the 5'-phosphate may be substantially less than the reported formal dianionic charge. Either way, the data provide evidence for the rather weak electrostatic interaction between a charged group at this site and the anionic flavin hydroquinone. In contrast, Esq/hq reported for the apoflavodoxin-riboflavin complex, which lacks the 5'-phosphate group, is 180 mV less negative than that of the native flavodoxin. The re-evaluation of the redox and cofactor binding properties of the riboflavin complex generated values for the dissociation constants for the riboflavin complex in the oxidized, semiquinone, and hydroquinone oxidation states that are 2100-, 63000-, and 54-fold higher, respectively, than that for the naturally occurring flavin mononucleotide complex. The large redox potential shifts observed for both redox couples in the riboflavin complex are primarily the consequence of a decreased stabilization of the semiquinone rather than the result of the absence of the negative charge of the 5'-phosphate. It is concluded from this study that the negative charge on the phosphate group of the cofactor does not play a disproportionate role in decreasing Esq/hq, at most contributing equivalently with the acidic amino acid residues clustered around the flavin to an unfavorable electrostatic environment for the formation of the flavin hydroquinone anion.

Apoproteins↗
PubMed1996

Chylomicron assembly and catabolism: role of apolipoproteins and receptors.

Chylomicrons are lipoproteins synthesized exclusively by the intestine to transport dietary fat and fat-soluble vitamins. Synthesis of apoB48, a translational product of the apob gene, is required for the assembly of chylomicrons. The apob gene transcription in the intestine results in 14 and 7 kb mRNAs. These mRNAs are post-transcriptionally edited creating a stop codon. The edited mRNAs chylomicrons from the shorter apoB48 peptide remains to be elucidated. In addition, the roles of proteins involved in the assembly pathway, e.g. apobec-1, MTP and apoA-IV, needs to be studied. Cloning of enzymes involved in the intestinal biosynthesis of triglycerides will be crucial to fully appreciate the assembly of chylomicrons. There is a need for cell culture and transgenic animal models that can be used for intestinal lipoprotein assembly. The catabolism of chylomicrons is far more complex and efficient than the catabolism of VLDL. Even though the major steps involved in the catabolism of chylomicrons are now known, the determinants for apolipoprotein exchange, processing of remnants in the space of Disse, as well as the mechanism of uptake of these particles by extra-hepatic tissue needs further exploration.

Animals↗
PubMed1996

Amperometric detection of quantal secretion from patch-clamped rat pancreatic beta-cells.

Serotonin (5-HT) is taken up in insulin granules and co-released with insulin on stimulation of pancreatic islet beta-cells. Based on these observations, we have used microcarbon fiber amperometry to examine secretogogue-induced 5-HT release from rat beta-cells preloaded for 4-16 h with 5-HT and then exposed to a bath solution containing 10 microM forskolin. In response to local application of KCl (60 mM) or tolbutamide (50-200 microM), we recorded barrages of amperometric events. Each amperometric event consisted of a short pulse of current measurable at electrode voltages that catalyze 5-HT oxidation. With either secretogogue, release was calcium-dependent. On combining amperometry with perforated patch whole-cell recording, we found that barrages of such events were well coupled in time and graded in intensity with depolarization-induced Ca2+ currents and well correlated with increases in membrane capacitance. In cell-attached patch recording, amperometric events evoked by application of tolbutamide followed the closure of ATP-sensitive K+ channels and coincided with the onset of electrical activity. These experiments suggest that amperometry is a useful technique for studying, in real time, the dynamic aspects of stimulus-secretion coupling in beta-cells. Their performance was facilitated by the design of a new carbon fiber electrode (ProCFE) described within.

Animals↗
PubMed1996

DNA index by image analysis in advanced endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries, affecting an estimated 140,000 women. More than 32,000 women will be diagnosed with endometrial cancer this year in the United States, and approximately 6,000 will die from this disease. METHODS: Twenty consecutive patients, surgically treated, with advanced endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, as well as FIGO stage, grade, and histology. DI was determined using image analysis. RESULTS: Ten of the 20 patients had recurrence of their disease within the 3-year observation period of the study. A DI of > or = 1.2 strongly predicted recurrence of disease (P = 0.002). Increasing histologic grade and an increasing DI were related (P = 0.01). CONCLUSION: Independent of other prognostic indicators, including lymphovascular space invasion, depth of invasion, and histologic type, a tumor with a DI of > or = 1.2, had a significantly increased chance of recurring within the 3-year observation period.

Aged↗
PubMed1996

Technicon Immuno 1 PSA assay measures both free and alpha-1-antichymotrypsin-complexed prostate-specific antigen on an equimolar basis.

In this study, we investigated the immunoreactivity of the Technicon Immuno 1 PSA assay, a monoclonal-polyclonal sandwich immunoassay, with free and ACT-complexed PSA. Assay calibrators prepared with free PSA (standard Immuno 1 calibrators) and calibrators consisting of 90% ACT-complexed and 10% free PSA (90:10 calibrators) yielded virtually identical PSA recoveries at all concentrations tested. Concentrations of total PSA at approximately 4 and 10 ng/mL, prepared in varying ratios of free PSA to PSA-ACT complex, recovered from 92-104% at 4 ng/mL and from 98-102% at 10 ng/mL. Additionally, an excellent correlation of serum total PSA values from a panel of 40 prostatic cancer patient samples was obtained using calibration curves generated with the standard Immuno 1 calibrators or the 90:10 calibrators. These results demonstrate that the Technicon Immuno 1 PSA assay measures free and ACT-complexed PSA on an equal molar basis.

Automation↗
PubMed1996

p53 as a prognostic indicator in endometrial cancer.

BACKGROUND: One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. Although endometrial cancer is the most common gynecologic malignancy in the United States, any connection between it and p53 is just beginning to be explored. METHODS: Forty-six consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. RESULTS: Thirty-five patients had endometrioid adenocarcinomas, 3 had adenosquamous carcinomas, 3 had papillary serous carcinomas, 3 had clear cell carcinomas, and 2 had undifferentiated carcinomas. p53 expression ranged from 0.0 to 55.8% with a mean of 10.7% for the cohort. For the patients with endometrioid carcinomas, the mean p53 expression was 3.9%, while for those with more aggressive histologies it was 32.4% (P < 0.001). Sixteen of the 35 endometrioid tumors (45.7%) stained positive for p53, while 11 of the remaining 12 (91.2%) tumors with more aggressive histologies stained positive (P < 0.01). Increasing histologic grade correlated with an increasing p53 expression (P = 0.006). The percentage of patient tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.01). However, the mean p53 expression was not different between early (stage 1) and advanced (stage 11, III, and IV) cancers (P = 0.55). Utilizing recurrence as the endpoint for multivariate analysis, FIGO stage and p53 expression were the only independent prognostic indicators found. CONCLUSION: p53 expression is more common in more aggressive histologic subtypes than in endometrioid adenocarcinomas. It is an independent prognostic indicator of disease recurrence.

Adult↗
PubMed1996

Proliferation index determined by MIB-1 and recurrence in endometrial cancer.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Stage, grade, DNA index, histologic type, depth of invasion, steroid receptor status, and the presence of positive peritoneal cytology have all been linked to survival. The monoclonal antibody MIB-1 reacts with the same antigen as Ki-67 giving an estimate of proliferation index. The authors investigated whether MIB-1 staining, using image analysis, could be used as a prognostic indicator of recurrence in endometrial carcinoma. METHODS: The tumors from 39 consecutive patients receiving primary surgical therapy for endometrial cancer were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. The patients were followed for a median of 34 months and their charts were reviewed to determine recurrence, histologic type, grade, stage, depth of invasion, and status of peritoneal cytology. RESULTS: Eleven of the 39 patients had recurrence of their disease within the 3-year observation period of this study. Overall, 22 patients had stage I disease, 3 patients had stage II disease, 12 patients had stage III disease, and 2 patients had stage IV disease. MIB-1 staining was not significantly elevated in advanced (stage III and IV) as opposed to early (stage I and II) cancers (P = 0.558). Elevated MIB-1 staining was associated with an increased incidence of recurrence within 24 months of diagnosis (P = 0.002). Patients whose tumors had MIB-1 staining of greater than or equal to 39.0% had an increased chance of recurring over patients whose tumors stained less than 39.0% (P = 0.003). CONCLUSION: In this series of 39 patients with endometrial cancers, MIB-1 monoclonal antibody staining was shown to be a prognostic indicator of recurrence.

Analysis of Variance↗
PubMed1996

Markov texture parameters as prognostic indicators in endometrial cancer.

BACKGROUND: Texture is a descriptive property of a surface distinct from color and shape. Image analysis allows gray-scale images to have their optical texture measured and analyzed. The authors, utilizing image analysis, prospectively studied Markov texture parameters to determine their relevance as prognostic indicators of disease recurrence in endometrial cancer. METHODS: Seventy-four consecutive patients, surgically treated, with endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as 21 Markov parameters. DI and the Markov parameters were quantified using image analysis. RESULTS: Median follow-up for the study population was 31 months with a range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12 patients died from disease during the observation period of the study. Eleven Markov parameters showed significant correlation with increasing FIGO stage (P < 0.05), while 14 Markov parameters showed significant correlation with survival (P < 0.05). Three Markov parameters, difference entropy (P = 0.025), information measure B (P = 0.01), and diagonal moment (P = 0.046), were demonstrated to be independent prognostic indicators along with the more traditional prognostic indicators, stage (P = 0.006), grade (P = 0.029), and depth of myometrial invasion (P = 0.03). CONCLUSION: Image analysis is able to quantify optical texture. Utilizing bivariate correlations and multivariate analysis, three of these parameters were demonstrated to be independent prognostic indicators in endometrial cancer, specifically difference entropy, information measure B, and diagonal moment.

Adult↗
PubMed1996

Heterogeneity of the glutathione transferase genes encoding enzymes responsible for insecticide degradation in the housefly.

One of the four glutathione-S-transferases (GST) that is overproduced in the insecticide-resistant Cornell-R strain of the housefly (Musca domestica) produces an activity that degrades the insecticide dimethyl parathion and conjugates glutathione to lindane. In earlier work, it was shown that the resistant Cornell-R carries an amplification, probably a duplication, of one or more of its GST loci and that this amplification is directly related to resistance. Using polymerase chain reaction (PCR) amplification with genomic DNA, multiple copies of the gene encoding the parathion-degrading activity (called MdGst-3) were subcloned from both the ancestral, insecticide-susceptible strain BPM and from the insecticide-resistant Cornell-R. In BPM, three different MdGst-3 genes were identified while in Cornell-R, 12 different MdGst-3 sequences were found that, though closely related to ancestral genes, had diverged by a few nucleotides. This diversity in MdGst-3 genomic sequences in Cornell-R is reflected in the expressed sequences, as sampled through a cDNA bank. Population heterozygosity cannot account for these multiple GST genes. We suggest that selection for resistance to insecticides has resulted in not only amplification of the MdGst-3 genes but also in the divergence of sequence between the amplified copies.

Animals↗
PubMed1996

[Study of an ancient corpse of the Warring States period unearthed from Tomb No. 1 at Guo-Jia Gang in Jingmen City (A comprehensive study)].

An ancient female corpse excavated from the robbed tomb No. 1 at Guo-Jia-Gang in Jingmen city of Hubei Province was studied. It was confirmed that the corpse was buried more than 2,300 years ago, namely at the middle stage of the Warring States period and is the earliest one of the ancient coffin corpses unearthed in China so far. It is of the same type as the ancient corpses of Weatern Han Dynasty excavated from tomb No. 1 at Ma-Wang-Dui in Changsha City and from the tomb No. 168 at Phoenix Hill in Jinagling City respectively. The collagenous fibers of connective tissue from all parts in the corpse were well preserved, showing fine ultrastructure with clear periodical cross banding, and a lot of bacterial spores were found between them. In addition, a large number of eggs of clonorchis sinensis and trichuris trichiura were found in the content of the bowel. The level and the cause of good preservation were discussed and it was believed that the good preservation may result from the combined effect of the internal and external environmental factors around the corpse.

Animals↗
PubMed1996

Rapid fluctuations in transmitter release from single vesicles in bovine adrenal chromaffin cells.

Single-vesicle release of catecholamines from chromaffin cells can be detected in real time as current spikes by the electrochemical method of amperometry. About 70% of spikes are preceded by a small "foot," the trickle of transmitter out of the early fusion pore. In addition, 20-50% of foot signals exhibit rapid fluctuations that we interpret as flickering of the fusion pore. There are also "stand-alone" foot signals, which may reflect transient fusions, in which the vesicles do not collapse completely into the plasma membrane. The number and frequency of the foot flickering are affected by intracellular Ca2+ concentration.

Animals↗
PubMed1996

In vitro assessment of variables affecting the efficiency and efficacy of adenovirus-mediated gene transfer to cystic fibrosis airway epithelia.

Primary cultures of airway epithelia were used to evaluate variables pertinent to adenovirus (Ad)-mediated gene transfer efficiency and efficacy including: (i) Ad-vectors with different promoters, (ii) the duration of vector incubation with cells, (iii) the concentration and depth of vector-containing medium at constant multiplicity of infection (moi) (10(3)), and (iv) the relative sensitivity of reverse transcription polymerase chain reaction (RT-PCR) versus functional analysis for the detection of transduced cystic fibrosis transmembrane conductance regulator (CFTR). An Ad5-lacZ vector with a cytomegalovirus (CMV) enhancer/promoter transduced the greatest amount of beta-galactosidase (beta-Gal) activity, while an Ad2-lacZ vector with an E1a enhancer/promoter transduced the least. Ad5-lacZ vectors with the Rous sarcoma virus (RSV), E1a/RSV, or CMV enhancer/beta-actin (CB) promoters transduced intermediate levels of beta-Gal. Optimal gene transfer efficiency was detected with a 4-8 hr incubation of Ad5-CMVlacZ with cells, although optimal CFTR Cl-transport function was detectable after only a 30 min incubation of Ad5-CBCFTR with cells, consistent with correction of > or = 6-10% of cells in the epithelial sheet. Ad5-CBCFTR transduction of CF airway epithelial cells (moi = 10(3)) was optimal when higher concentrations, lower volumes, or smaller depths of vector-containing medium were utilized. RT-PCR was at least 100-fold more sensitive for the detection of transduced CFTR than functional analysis, and could detect as few as 0.001% Ad5-CBCFTR-infected CF cells admixed with uninfected CF cells. In summary, the variables studied clearly affect the efficiency of Ad-mediated gene transfer in vitro and potentially in vivo. They also suggest that RT-PCR is a poor marker of gene transfer efficiency and efficacy.

Adenoviruses, Human↗