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Biomedical subjects

D Zhang

Publications and source records attributed to D Zhang.

At least 91 records · Page 5Linked to original sources

Derivative hydride generation atomic absorption spectrometry and determination of lead traces in waters.

Fundamentals of derivative hydride-generation atomic absorption spectrometry (DHGAAS) are described. A linear relationship was obtained between the derivative absorbance and the concentration of analysis in a sample. The new DHGAAS method was applied to the determination of traces of lead in water. The conditions affecting the derivative absorbance of lead were evaluated and optimized. The detection limit and sensitivity of the proposed method were 26 times and 8.8 times better, respectively, than those of conventional hydride-genera-tion atomic absorption spectrometry. The characteristic concentration (for a derivative absorbance of 0.0044) and detection limit (3sigma) for lead were 0.017 and 0.096 ng mL(-1), respectively, for a 2 mV min(-1) sensitivity range setting. The recovery range was 92.5-103%.

Acids↗

Polymorphism of the thrombostasin gene in the horn fly (Haematobia irritans) revealed in a cDNA library and in genomic DNA.

Thrombostasin (TS) is a newly described thrombin-inhibiting protein isolated from the saliva of the horn fly (Haematobia irritans), a blood-sucking ectoparasite of cattle. This report provides a detailed characterization of the TS gene and the first analysis of the allelic complexity of a gene for an anti-hemostatic protein from a blood-feeding insect. Multiple point mutations at fixed positions in the TS gene were identified in a cDNA library prepared from mRNA isolated from horn fly salivary glands. When translated, the variant mRNAs would specify five biochemically active peptides that differ in molecular weight, isoelectric point and predicted secondary structure. Allelic variation with the same mutation pattern was revealed in the genomes of individual flies collected in the field and sampled from a long-standing laboratory colony. Approximately 60% of flies examined carried heterozygous alleles, including five additional alleles not found in the cDNA library. Comparative analysis of the allelic mutations and the predicted effects on secondary structures of the active proteins produced suggest that the TS gene may be undergoing evolutionary selection.

Amino Acid Sequence↗

Results of surgical resection of patients with primary lung cancer: a retrospective analysis of 1,905 cases.

BACKGROUND: Surgical resection, combined therapies, and lymphadenectomy are extensively utilized in the treatment of patients with lung cancer. In the present study, we summarized the clinical data of patients with primary lung cancer after surgical resection alone or combined with adjuvant therapy, and evaluate the main factors influencing long-term survival. METHODS: A retrospective review of 1,905 consecutive patients with primary lung cancer treated at the Cancer Institute of the Chinese Academy of Medical Sciences from March 1961 through December 1995 was performed. Statistical analysis was done using STATA software. The survival rate was estimated using the life-table method. Survival differences were performed using the log-rank test. The modified 1997 TNM staging system was used. RESULTS: There was a 12.28% morbidity rate and a 1.31% hospital mortality in our series. The 5-year survival rate for the complete resection was 49.5% and for the palliative resection 18.8% (p < 0.01). The 5-year survival rate was 72.0% in stage IA and 61.0% in stage IB (p < 0.05), 32.9% in stage IIA and 34.5% in stage IIB, 22.6% in stage IIIA and 15.9% in stage IIIB (p < 0.05), and 7.1% in stage IV. CONCLUSIONS: Multiple factors influence the long-term survival of patients with primary lung cancer after surgery. They include TNM staging, the extent of surgical resection (complete or palliative), resection margin (positive or negative), pathologic type of tumors, and type of resection.

Adult↗

Structure and function of GABA(C) receptors: a comparison of native versus recombinant receptors.

In less than a decade our knowledge of the GABA(C) receptor, a new type of Cl(-)-permeable ionotropic GABA receptor, has greatly increased based on studies of both native and recombinant receptors. Careful comparison of properties of native and recombinant receptors has provided compelling evidence that GABA receptor rho-subunits are the major molecular components of GABA(C) receptors. Three distinct rho-subunits from various species have been cloned and the pattern of their expression in the retina, as well as in various brain regions, has been established. The pharmacological profile of GABA(C) receptors has been refined and more specific drugs have been developed. Molecular determinants that underlie functional properties of the receptors have been assigned to specific amino acid residues in rho-subunits. This information has helped determine the subunit composition of native receptors, as well as the molecular basis underlying subtle variations among GABA(C) receptors in different species. Finally, GABA(C) receptors play a unique functional role in retinal signal processing via three mechanisms: (1) slow activation; (2) segregation from other inhibitory receptors; and (3) contribution to multi-neuronal pathways.

Animals↗

An optimized system for studies of EPO-dependent murine pro-erythroblast development.

OBJECTIVE: Objectives were to develop new means to isolate useful numbers of primary progenitor cells and to quantitatively assay the stepwise maturation of erythroblasts. METHODS: Approaches involved dosing mice with thiamphenicol (TAP) to yield staged cohorts of pro-erythroid cells; optimizing conditions for their EPO-dependent in vitro growth and survival; developing assays for CFU-E maturation; analyzing stage-specific transcript expression; and expressing a heterologous, erythroid-specific tag (EE372) in transgenic mice. RESULTS: Per TAP-treated mouse, 3 x 10(7) highly EPO-responsive erythroid progenitor cells were generated that represented up to 30% of total splenocytes and showed strict dependence on EPO for survival, growth, and immediate response gene expression. In this developing cohort, a tightly programmed sequence of gene expression was observed, and maximal expression of c-kit, EPO receptor, and beta-globin transcripts occurred at 72, 96, and 120 hours post-TAP withdrawal, respectively. Also, the newly discovered erythroid-specific dual-specificity kinase, DYRK3, was revealed to be expressed at a late CFU-E stage. In vitro, these progenitor cells matured stepwise from high FALS Ter119- cells (24-hour culture) to high FALS Ter119+ cells (24-36 hours) to low FALS Ter119+ maturing erythroblasts (40-48 hours) and sharp differences in their morphologies were observed. Finally, a MACS-based procedure for the purification of erythroid progenitor cells from TAP-treated EE372 transgenic mice also was developed. CONCLUSIONS: A comprehensive new system for isolating large numbers of primary murine erythroid progenitor cells and quantitatively monitoring their development is established that should serve well in investigations of endogenous and pharmacological regulators of red blood cell development.

Animals↗

Experimental imaging of the acoustic nonlinearity parameter B/A for biological tissues via a parametric array.

The acoustic nonlinearity parameter B/A is an important parameter in nonlinear acoustics and has been suggested to be a novel parameter for ultrasound tissue characterization. In this paper, the principle and experimental results for B/A imaging by using a parametric array are presented. As two primary waves with different frequencies are radiated simultaneously from a circular piston source, a secondary wave at the difference frequency is generated due to the nonlinear interaction of the two primary waves. The axial sound pressure amplitude curve for the generated difference frequency wave in the near field is measured and agrees well with the theoretical calculation. Unlike the second harmonic wave, the difference frequency component of the parametric array grows almost linearly with distance from the piston source and goes through fewer oscillations in the near field. It therefore provides a better source for acoustic nonlinearity parameter tomography. On the basis of the finite amplitude insert substitution method and the conventional CT technology, an experimental imaging system for acoustic nonlinearity parameter B/A via a parametric array is set up. B/A images for several biological specimens, including normal and pathological tissues, are obtained.

Acoustics↗

The pressor response to acute hyperlipidemia is enhanced in lean normotensive offspring of hypertensive parents.

Family history is an important predictor of the cardiovascular risk factor cluster associated with insulin resistance. The dyslipidemia associated with insulin resistance may contribute to elevated blood pressure (BP). This study was undertaken to further explore the link between family history, dyslipidemia, and BP regulation. Twenty-three lean normal volunteers with a negative family history (FH-, n = 11) or positive family history (FH+, n = 12) of hypertension were evaluated under baseline conditions and during a 4-h infusion of intralipid and heparin (acute hyperlipidemia). Fasting blood was drawn for lipids including nonesterified fatty acids (NEFA). After 2 and 4 h of intralipid and heparin, blood was drawn for NEFA. The BP was measured at baseline and every 30 min after starting the intralipid and heparin infusion. Baseline triglycerides and very low density lipoprotein cholesterol concentrations were higher in FH+ than FH- subjects (P < .05). However, NEFA increased similarly in both groups during the infusion of intralipid and heparin. The BP and heart rate increased with acute hyperlipidemia in all subjects combined (P < .05). Despite the similar increase of NEFA, mean BP, pulse pressure, and pressure-rate product increased significantly in FH+ subjects but not in FH- volunteers with acute hyperlipidemia. Although systolic BP increased in both groups, the increase was greater in FH+ than in FH- volunteers during acute hyperlipidemia (14 +/- 2 v 10 +/- 2 mm Hg, P < .05). These results suggest that higher plasma lipids combined with a greater pressor response to hyperlipidemia may contribute to the development of high BP in subjects with a family history of hypertension.

Acute Disease↗

Cell- and stage-specific high-level expression of TBP-related factor 2 (TRF2) during mouse spermatogenesis.

Mice lacking the TBP-related factor 2 (TRF2) gene, which is highly expressed in the testis, have a severe defect in spermiogenesis. Here we show that the expression of TRF2 is both cell type- and stage-specific. TRF2 expression was first detected in the late pachytene spermatocytes at stage VIII and increased throughout the subsequent stages. After meiotic divisions, the TRF2 expression declined continuously in round spermatids during progression from stage I to stage V. This observation is consistent with an essential regulatory role of TRF2 in male germ cell differentiation during spermatogenesis.

Animals↗

Manduca sexta IRP1: molecular characterization and in vivo response to iron.

Manduca sexta IRP1 was cloned and sequenced. The deduced amino acid sequence of Manduca IRP1 shows high similarity to other IRP1 proteins. The Cys residues required as ligands for the iron sulfur cluster, as well as all residues necessary for aconitase activity are conserved in the insect protein. Purified recombinant Manduca IRP1 binds specifically to transcripts of the iron responsive element (IRE) of Manduca or human ferritin subunit mRNA. Binding activity of the recombinant protein was not influenced by the presence of beta-mercaptoethanol. However, IRP/IRE binding activity of cytoplasmic extracts from fat body was decreased by reducing agents in a dose-responsive manner. Fat body IRP1/IRE binding activity was reduced for Manduca sexta larvae injected with low doses of iron, while IRP1 mRNA and protein levels remained stable. At higher iron doses, binding activity increased and stabilized. Hemolymph ferritin levels showed an inverse relationship to IRP1/IRE binding activity. These data suggest that the Manduca IRP1 is likely involved in translational control of ferritin synthesis in a manner similar to that found in vertebrates. However, factors other than iron can influence IRP/IRE interaction and hemolymph ferritin levels in insects.

Animals↗

A biochemical function for the Sm complex.

Within the yeast commitment complex, SmB, SmD1, and SmD3 make direct contact with the pre-mRNA substrate, close to the 5' splice site. Only these three Sm proteins have long and highly charged C-terminal tails, in metazoa as well as in yeast. We replaced these proteins with tail-truncated versions. Genetic assays demonstrate that the tails contribute to similar and overlapping functions, and cross-linking assays show that the tails make direct contact with the pre-mRNA in a largely sequence-independent manner. Other biochemical assays indicate that they function at least in part to stabilize the U1 snRNP-pre-mRNA interaction. We speculate that this role may be general, and may have even evolved to aid weak intermolecular nucleic acid interactions of only a few base pairs.

Amino Acid Sequence↗

Comparison of volatiles, phenolics, sugars, antioxidant vitamins, and sensory quality of different colored carrot varieties.

Four different colored carrots, orange, purple with orange core, yellow, and white, were examined for their content of phenolics, antioxidant vitamins, and sugars as well as their volatiles and sensory responses. A total of 35 volatiles were identified in all carrots, 27 positively. White carrot contained the highest content of volatiles, followed by orange, purple, and yellow. In total, 11, 16, 10, and 9 phenolic compounds were determined for the first time in orange, purple, yellow, and white carrots, respectively. Of these, chlorogenic acid was the most predominant phenolic compound in all carrot varieties. Differences (p < 0.05) in relative sweetness, the contents of vitamin C and alpha- and beta-carotenes, and certain flavor characteristics were observed among the colored carrot varieties examined. Purple carrots contained 2.2 and 2.3 times more alpha- and beta-carotenes (trace in yellow; not detected in white) than orange carrots, respectively. Purple carrot may be used in place of other carrot varieties to take advantage of its nutraceutical components.

Antioxidants↗

Microtubule disruption modulates the Rho-kinase pathway in vascular smooth muscle.

Microtubules constitute one of the main cytoskeletal components in eukaryotic cells. Recent studies have shown that microtubule disruption induced significant vasoconstriction or enhanced agonist-induced contraction in vascular smooth muscle. However, the underlying mechanisms are not clear. We hypothesize that microtubule disruption may affect contractile signaling in vascular smooth muscle and lead to the enhanced contraction. The present study demonstrates that both colchicine and nocodazole induced a small but sustained contraction (4-6% P0) in rat aortic rings. This microtubule disruption-induced contraction was abolished by co-treatment with either HA 1077 or Y-27632, both of which are relatively specific Rho-kinase inhibitors. However, co-treatment with ML-9, an inhibitor of myosin light chain kinase, (MLCK) did not have a significant effect on the colchicine-induced contraction. The enhanced KCl-induced contraction due to treatment with colchicine was also blocked by inhibition of Rho-kinase, but not by inhibition of MLCK. These results indicate that microtubule disruption modulates contractile signaling in vascular smooth muscle, mainly through the Rho-kinase pathway, but not MLCK. Interestingly, the colchicine-enhanced, phenylephrine-induced contraction was not completely blocked by inhibition of Rho-kinase suggesting that other signaling pathways might also be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Impact of the intramitochondrial enzyme organization on fatty acid oxidation.

The enzymes of mitochondrial beta-oxidation are thought to be organized in at least two functional complexes, a membrane-bound, long-chain-specific beta-oxidation system and a matrix system consisting of soluble enzymes with preferences for medium-chain and short-chain substrates. This hypothesis is supported by the observation that the inactivation of long-chain 3-ketoacyl-CoA thiolase by 4-bromotiglic acid (4-bromo-2-methylbut-2-enoic acid) causes the complete inhibition of palmitate beta-oxidation even though 3-ketoacyl-CoA thiolase, which acts on 3-ketopalmitoyl-CoA, remains partly active. The observed substrate specificities of long-chain acyl-CoA dehydrogenase (LCAD) and very-long-chain acyl-CoA dehydrogenase prompt the suggestion that LCAD is a functional component of the long-chain-specific beta-oxidation system. Altogether, a view is emerging of the organization of beta-oxidation enzymes in mitochondria that supports the idea of intermediate channelling and explains the apparent absence of true intermediates of beta-oxidation from mitochondria.

Acyl-CoA Dehydrogenase↗

Repression of Manduca sexta ferritin synthesis by IRP1/IRE interaction.

Mammalian ferritin subunit synthesis is controlled at the translational level by the iron regulatory protein 1 (IRP1)/iron responsive element (IRE) interaction. Insect haemolymph ferritin subunit messages have an IRE in the 5'-untranslated region (UTR). We have shown that recombinant M. sexta IRP1 represses the in vitro translation of both the heavy and light chain ferritin subunits from this species without altering transcription. Deletion of either the 5'-UTR or the IRE from the mRNA abolishes IRP1 repression. Our studies indicated that the translational control of ferritin synthesis by IRP/IRE interaction could occur in insects in a manner similar to that of mammals. To our knowledge, this is the first report of the control of insect ferritin synthesis by IRP1/IRE interaction. Furthermore, this is the first indication that the synthesis of a secreted ferritin subunit can also be controlled in this manner.

Amino Acid Sequence↗

Effect of multiple mutations in the core promoter and pre-core/core region of hepatitis B virus genome on the response to interferon in e antigen-positive chronic hepatitis B.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) genomic mutations may be one of the factors that influence the efficacy of interferon (IFN) therapy. The aim of this study was to investigate the effects of mutations in different parts of the HBV genome on IFN therapy. METHODS: We studied the baseline clinical, biochemical, serologic and virologic parameters in 17 patients with e antigen-positive chronic hepatitis B. The DNA sequence of the X gene and pre-core/core gene in serum samples of these patients was analyzed before the initiation of IFN therapy. RESULTS: All five patients with the T1762-A1764 mutation were IFN responsive, while among the 12 remaining patients, only two responded to therapy. Among five patients with both a pre-core A1896 mutation and a mutation in the epitope aa 107-118 of the core region, four were non-responders whereas the fifth responded to therapy. In three other patients with A1896 mutations, one with simultaneous mutations in five lymphocytic epitopes did not respond to therapy; the two remaining patients with concomitant mutations in one or two epitopes were responsive. Serum HBV-DNA levels were lower and titers of antibody to hepatitis B virus core antigen-immunoglobin M (anti-HBc-IgM) were higher in the responders than in the non-responders. Hepatitis B virus genotypes B and C were found to be in all these Chinese patients. CONCLUSIONS: These results suggest that HBV genomic mutations, serum viral loads and titers of anti-HBc-IgM might be predictive of the efficacy of IFN therapy. These clinical findings should be further investigated by in vivo and in vitro experiments.

Adult↗

The midline thalamus: alterations and a potential role in limbic epilepsy.

PURPOSE: In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy. METHODS: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. RESULTS: The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration. CONCLUSIONS: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits.

Anatomy, Cross-Sectional↗

A traffic sign recognition test can discriminate between older drivers who have and have not had a motor vehicle crash.

OBJECTIVES: To determine whether a Traffic Sign Recognition Test (TSRT) can identify older drivers who recently had a motor vehicle crash (MVC). DESIGN: Retrospective, matched, case-control study. SETTING: Licensed drivers in Galveston, Texas. PARTICIPANTS: 60 crash and 60 control subjects matched for age and gender. Cases were identified from accident records. Controls were selected from a randomized list of licensed drivers in Galveston. MEASUREMENTS: Folstein Mini-Mental State Examination (MMSE) and the TSRT. RESULTS: A TSRT significantly distinguished between case and control groups (P = .01). The MMSE did not (P = .61). A TSRT predicted MVC in a multivariate analysis controlling for education, MMSE score, race/ethnicity, and mileage driven/year (odds ratio = 0.88, 95% confidence interval = 0.77-1.00). CONCLUSION: A TSRT successfully identifies older drivers with a recent MVC, but the test lacks sensitivity and specificity. A prospective study is needed to further delineate the TSRT's usefulness in predicting crash risk in older drivers.

Accidents, Traffic↗