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Biomedical subjects

Z Lu

Publications and source records attributed to Z Lu.

At least 415 records · Page 23Linked to original sources

Characterization of the pea chloroplast DNA OriA region.

One of the two origins of replication in pea chloroplast DNA (oriA) maps in the rRNA spacer region downstream of the 16S rRNA gene, and further characterization of this origin is presented here. End-labeling of nascent DNA strands from in vivo replicating ctDNA was used to generate probes for Southern hybridization. Hybridization data identified the same region that was previously mapped to contain D-loops by electron microscopy. Subclones of the oriA region were tested for their ability to support in vitro DNA replication using a partially purified pea ctDNA replication system. Two-dimensional agarose gel electrophoresis identified replication intermediates for clones from the region just downstream of the 16S rRNA gene, with a 450-bp SacI-EcoRI clone showing the strongest activity. The experiments presented in this paper identify the 940 base pair region in the rRNA spacer between the 3' end of the 16S rRNA gene and the EcoRI site as containing oriA. Previous studies by electron microscopy localized the D-loop in the spacer region just to the right of the BamHI site, but the experiments presented here show that sequences to the left of the BamHI site are required for replication initiation from oriA. DNA sequence analysis of this region of pea ctDNA shows the presence of characteristic elements of DNA replication origins, including several direct and inverted repeat sequences, an A + T rich region, and dnaA-like binding sites, most of which are unique to the pea ctDNA oriA region when compared with published rRNA spacer sequences from other chloroplast genomes.

Base Sequence↗

Acoustic response properties of single units in the torus semicircularis of the goldfish, Carassius auratus.

Single units of the goldfish torus semicircularis (TS) were recorded in response to pure tones. Response areas (RA) were obtained by recording the number of spikes evoked by tones in a range of frequencies and levels within the units' dynamic range. RAs gave estimates of best sensitivity (BS), characteristic frequency (CF), most excitatory frequency at each level (BF), and Q10dB. Peri-stimulus-time histograms (PSTH), interspike interval histograms (ISIH), and period histograms were obtained at various frequencies and levels to describe the units' temporal response patterns. The distribution of CF is nonuniform with modes at 155, 455, and 855 Hz. The distribution of the coefficient of synchronization to standard tones is also nonuniform, revealing a dichotomy between units with little or no phase-locking and those that phase-lock strongly. PSTHs for units without significant phase-locking vary widely and include patterns resembling those of the mammalian auditory brainstem. Compared with saccular afferents, torus units tend to have lower spontaneous rates, greater sensitivity, and sharper tuning. Unlike saccular afferents, BF is independent of level for most torus units. Some torus units are similar to saccular afferents while others reveal significant transformations of information between the periphery and the midbrain.

Acoustic Stimulation↗

Three adjacent genes of African swine fever virus with similarity to essential poxvirus genes.

Nucleotide sequencing of the right end of the SalIj fragment of the highly virulent Malawi Lil20/1 strain of African swine fever virus (ASFV) has revealed three adjacent genes with similarity to: serine-threonine protein kinases; members of the putative helicase superfamily SF2; and the vaccinia virus 56 kDa abortive late protein. All three genes are transcribed to the left with respect to the orientation of the ASFV genome. Gene L19IL predicts a protein similar to serine-threonine protein kinases including vaccinia virus gene B1R. Gene L19KL predicts a protein that is likely to be a nucleic acid-dependent ATPase, as it has similarity to both the poxvirus 70 kDa early transcription factor subunit and the poxvirus nucleoside triphosphatase I gene. Gene L19LL has extensive similarity to the vaccinia virus 56 kDa abortive late protein.

African Swine Fever Virus↗

Tension transients initiated by photogeneration of MgADP in skinned skeletal muscle fibers.

Addition of MgADP to skinned skeletal muscle fibers causes a rise in Ca(2+)-activated isometric tension. Mechanisms underlying this tension increase have been investigated by rapid photogeneration of ADP within skinned single fibers of rabbit psoas muscle. Photolysis of caged ADP (P2-1(2-nitrophenyl)ethyladenosine 5'-diphosphate) resulted in an exponential increase in isometric tension with an apparent rate constant, kADP, of 9.6 +/- 0.3 s-1 (mean +/- SE, n = 28) and an amplitude, PADP, of 4.9 +/- 0.3% Po under standard conditions (0.5 mM photoreleased MgADP, 4 mM MgATP, pH 7.0, pCa 4.5, 0.18 M ionic strength, 15 degrees C). PADP depended upon the concentration of photoreleased MgADP as well as the concentration of MgATP. A plot of 1/PADP vs. 1/[MgADP] at three MgATP concentrations was consistent with competition between MgADP and MgATP for the same site on the crossbridge. The rate of the transient, kADP, also depended upon the concentration of MgADP and MgATP. At both 4 and 1 mM MgATP, kADP was not significantly different after photorelease of 0.1-0.5 mM MgADP, but was reduced by 28-40% when 3.5 mM MgADP was added before photorelease of 0.5 mM MgADP. kADP was accelerated by about twofold when MgATP was varied from 0.5 to 8 mM MgATP. These effects of MgATP and MgADP were not readily accounted for by population of high force-producing states resulting from reversal of the ADP dissociation process. Rather, the results suggest that competition between MgADP and MgATP for crossbridges at the end of the cycle slows detachment leading to accumulation of force-generating crossbridges. Elevation of steady-state Pi concentration from 0.5 to 30 mM caused acceleration of kADP from 10.2 +/- 0.5 to 27.8 +/- 1.8 s-1, indicating that the tension rise involved crossbridge flux through the Pi dissociation step of the cycle.

Adenosine Diphosphate↗

Quantitative aspects of the mutant analysis by PCR and restriction enzyme cleavage (MAPREC).

Quantitation of virus revertants by PCR and restriction enzyme cleavage may give nonlinear results and, in some cases, produce artifacts caused by nucleotide misincorporation and heteroduplex formation, occurring during PCR. Modifications of the procedure allowed us to overcome these problems and develop a highly sensitive and reliable method of mutant quantitation. This procedure can be used to assess the quality of live vaccines and to study heterogeneity of viral and bacterial populations.

Base Sequence↗

The time of administration of 3'-azido-3'-deoxythymidine (AZT) determines its host toxicity with possible relevance to AZT chemotherapy.

3'-Azido-3'-deoxythymidine (AZT) is the drug most widely used in the treatment of AIDS. Its major drug-related toxicity is bone marrow suppression, which limits the dose of AZT that can be used. It is essential that AZT be phosphorylated for antiviral effect. We have recently demonstrated that thymidine kinase (TK), the initial enzyme in AZT anabolism, follows a circadian pattern in rat bone marrow. The present study was undertaken to determine whether AZT toxicity is related to the time of its administration and whether the variation in toxicity is correlated with the circadian variation in TK activity. Male Sprague-Dawley rats were housed under standardized conditions of light and dark (lights on 0600 to 1800 and lights off 1800 to 0600) for 4 weeks. The animals were randomly divided into seven groups; six groups were administered AZT by intraperitoneal injection at the same dose of 750 mg/kg of body weight at various times (0400, 0800, 1200, 1600, 2000, and 2400), and one group was used as a control. AZT-related toxic effects, including bone marrow toxicity, differed significantly among the treatment groups, depending on the time of AZT administration (by analysis of variance and Cosinor analysis, P < 0.001). The least toxicity was observed in rats receiving AZT at 1600 (10 h after light onset [10 HALO], in late sleep span) and the greatest toxicity was observed in those injected at 0400 (22 HALO, in late activity span). To verify these results, we administered AZT by intraperitoneal injection at an approximately 50% lethal dose (1,500 mg/kg) to two groups of rats, one at 1200 (6 HALO, in the middle of the sleep span) and the other at 2400 (18 HALO, in the middle of the activity span). AZT lethality was significantly higher in rats receiving AZT at 2400 (18 HALO, in the middle of the activity span). Further statistical analysis demonstrated that the variation in AZT toxicity was correlated with the circadian variation in TK activity in bone marrow of the same species (peak activity at 0400 [22 HALO, in late activity span] and trough activity at 1600 [10 HALO, in late sleep span]), suggesting that the circadian variation in TK activity may be the biochemical basis for the observed circadian variation in AZT toxicity. These results may be useful in the design of improved AZT chemotherapeutic regimens.

Analysis of Variance↗

An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1.

An open reading frame, LMW5-HL, in the African swine fever virus genome displays a high degree of similarity to the proto-oncogene bcl-2 and, to a lesser degree, the Epstein-Barr virus gene BHRF1. A highly conserved central region is found in all three proteins. LMW5-HL encodes a protein of 18 kDa that is present in infected porcine macrophages at both early and late times postinfection. The similarity of LMW5-HL to bcl-2 and BHRF1 suggests a role for it in cell maintenance during productive or persistent viral infection.

African Swine Fever Virus↗

Phase I trial of low-dose, prolonged continuous infusion fluorouracil plus interferon-alfa: evidence for enhanced fluorouracil toxicity without pharmacokinetic perturbation.

PURPOSE: To determine the maximum-tolerable dose (MTD) of fluorouracil (5-FU) administered as a low-dose, prolonged continuous intravenous infusion (PCI) plus interferon-alfa (IFN-alpha) that would permit treatment for at least 28 consecutive days, and to determine the effect of IFN-alpha on 5-FU pharmacokinetics. PATIENTS AND METHODS: Twenty-six assessable patients with advanced cancer received low-dose PCI 5-FU (150, 200, 250, and 300 mg/m2/d) plus IFN-alpha, 5 x 10(6) IU/m2 administered subcutaneously (SC) at hour 48 of the 5-FU infusion, then thrice weekly thereafter in cohorts of at least three patients. Treatment continued until treatment-limiting toxicity (TLT) developed, such as mucositis, diarrhea, or fatigue. Escalation to the next 5-FU dose level occurred if none of three or zero to two of six patients developed TLT before day 28. Quantitation of plasma 5-FU concentration by high-performance liquid chromatography was performed in 15 patients. Data were standardized using the Cosinor method and compared before and after IFN-alpha administration using the paired t test. RESULTS: The mean number of days of continuous 5-FU therapy for patients receiving 150, 200, 250, and 300 mg/m2/d of 5-FU plus IFN alfa-2a (IFN-alpha 2a) was 75, 54, 37, and 22 days, respectively. The MTD of PCI 5-FU by our criteria that could be combined with IFN-alpha was 250 mg/m2/d. Comparison of the standardized pharmacokinetic data showed no significant effect of IFN-alpha on plasma 5-FU concentration, and no alteration of the normal circadian variation in plasma 5-FU concentration that was evident before IFN-alpha administration. Objective response occurred in patients with adenocarcinoma of the pancreas (n = 3), kidney (n = 2), and lung (n = 1). CONCLUSION: IFN-alpha substantially enhanced the gastrointestinal toxicity of low-dose PCI 5-FU without affecting 5-FU pharmacokinetics, contrary to previous reports using alternative 5-FU schedules in which IFN-alpha-related enhancement of 5-FU toxicity was attributable to reduced 5-FU clearance. Our findings suggest that under certain conditions, mechanisms other than altered 5-FU pharmacokinetics may be responsible for the ability of IFN-alpha to enhance the toxic effects of 5-FU.

Adult↗

Hemodynamic effects of terazosin in congestive heart failure.

To determine the hemodynamic effects of a new alpha-1 blocker, terazosin, in congestive heart failure, 10 patients with this condition underwent hemodynamic testing at rest. Thirty minutes after the oral administration of 4 mg terazosin, mean right atrial pressure, mean pulmonary artery pressure and pulmonary capillary wedge pressure were found to be decreased, while the cardiac index was increased significantly. Improvement in hemodynamics persisted for more than 15 h, without an increase in heart rate. It is suggested that terazosin may have effective applications in the treatment of congestive heart failure.

Adolescent↗

[Effects of electroacupuncture at different frequencies on the nociceptive response and central contents of GABA and glutamic acid in arthritic rats].

It has been demonstrated that electroacupuncture (EA) produces analgesia in acute arthritic animal models, while the differential analgesic effects at different EA parameters remains to be discovered. In the present experiment, the effects of EA at 100 Hz and 15 Hz on bilateral Yanglingpuan acupoints of the arthritic rats was studied. The results showed: 1) 15Hz EA was more effective than 10Hz EA for analgesia; 2) spinal glutamic acid content of the 15-Hz EA group was significantly lower than that of the 100-Hz EA group, and 3) no significant difference in GABA contents between the two groups was found. The results suggest that spinal glutamic acid may be involved in the different analgesic effects of EA at different frequencies in arthritic rats.

Acupuncture Analgesia↗

[Effects of interfacial state and bonding on the biostrength of plat castable ceramics crown].

Plat castable ceramics (PCC) restorations depend primarily on their biostrength. In our experiment the human oral physiological environment was simulated and we studied the effects of restoration-tooth interfacial state and bonding on the biostrength of PCC crowns. The bond strength affects the biostrength of PCC crowns obviously. The interfacial treatment affects not only the bond strength between PCC crown and tooth structure but also the biostrength of the crown cemented.

Adhesives↗

Thymic carcinoid tumor--a report of 7 cases.

The thymic carcinoid tumor is a rare neoplasm which is often clinically misdiagnosed as thymoma. But the two differ in origin, biological behavior, accompanying syndromes, pathological features, and prognosis. The characteristics of the thymic carcinoid tumor are: difficulty in diagnosis, high malignancy, frequent recurrence and extrathoracic metastasis over a prolonged period postoperatively. Complete surgical resection of original and recurrent tumors is the important treatment. Microscopic, electron microscopic and immunohistochemical examinations may be required in making an accurate pathological diagnosis. This paper reports 7 cases of thymic carcinoid tumor.

Adult↗

[An investigation of the effect of rostral ventrolateral medulla lesion on pressor response induced by electrical stimulation of hypothalamic paraventricular nucleus in the cat].

The experiments were performed on 20 adult cats anesthetized with chloralose and urethane, paralyzed and artificially ventilated. The rostral ventrolateral medulla (RVL) was explored by electrical stimulation. We found that an area, 3-5 mm rostral to the obex, 3-4 mm lateral to the midline, and 0-1 mm from the ventral surface of the medulla, was the most effective region for producing a pressor response. After bilateral microinjection of kainic acid into or electrolytic lesion of the above-mentioned active RVL area, a large decrease in arterial blood pressure was elicited, and the pressor response induced by electrical stimulation of the hypothalamic paraventricular nucleus (PA) was nearly eliminated. The results suggest that the RVL mediates the PA pressor response.

Animals↗

[Study on the color modification buring surface staining of PLAT castable ceramic restorations].

The surface staining of castable ceramic restorations is a technique-dependent process. So it is inevitable that the color of restorations mismatch the color of natural teeth. This study was conducted to explore the possibility of modifying the color by selected use of special colored stains. Eighty PLAT castable ceramic samples were machined, 16 mm in diameter, 1.2 mm in thickness. Thirty-two samples were stained with yellow stain and 32 samples orange. Sixteen samples were stained with red, green, blue and violet stains, respectively. To the yellow and orange stained samples, we applied correspondingly the same stain, red, green, blue and violet stains. The color of each sample was evaluated with a colorimeter and translated to Munsell notations. The results indicated that chroma was intensified by each application of the same stain. Red and green stains made the hue reddish and greenish. Blue and violet stains could effectively decrease the chroma of yellow or orange. Meanwhile, the hue was also slightly changed to greenish and reddish.

Ceramics↗

Platelet activating factor-induced microvascular permeability increases in the cat hindlimb.

Changes in microvascular permeability induced by platelet activating factor (PAF) were measured in the isolated, perfused cat hindlimb preparation, and compared to the effect produced by another inflammatory mediator, histamine. Permeability was assessed from changes in the protein reflection coefficient, as measured from changes in hematocrit and protein concentration resulting from microvascular fluid filtration. The findings were 1) PAF produces transient increases in permeability similar to histamine, but PAF is approximately 30 times as potent; 2) the permeability changes induced by 76 nM PAF can be totally inhibited by the specific PAF receptor blocker WEB-2086, but the blocker can only partially inhibit 380 nM PAF, a dose that produces a maximal increase in permeability; 3) Diphenhydramine (2 microM), an H1-receptor blocker, totally inhibits the transient permeability increase produced by 2 microM histamine; 4) Cimetidine (2 or 20 microM), an H2 blocker, could not inhibit this latter increase; 5) Isoproterenol (1 microM), a beta-agonist, totally inhibited the permeability increase produced by 1 microM histamine, but 10 microM isoproterenol only partially inhibited the maximal permeability increase produced by 10 microM histamine; 6) Isoproterenol could not inhibit PAF's permeability effect; and 7) PAF's effects were unchanged by depletion of white blood cells in the perfusate. These results suggest that PAF and histamine work through different pathways to increase permeability, but the final step of endothelial contraction, which opens large inter-endothelial gaps, occurs in response to both mediators. In addition, when concentrations of these inflammatory agents are sufficient to produce maximal permeability increases, as can occur in shock situations, then the permeability increases are more sustained and resistant to receptor inhibition.

Animals↗

(Aminoalkoxy)chromones. Selective sigma receptor ligands.

A series of (aminoalkoxy)chromones has been prepared, members of which bind potently (16-100 nM) at the sigma binding site and bind weakly (greater than 1000 nM) at the dopamine D2 receptor and 33 other receptors, second messenger systems, and ion channels. At the sigma receptor, the preferred position of attachment for the aminoalkoxy side chain to the chromone ring followed the rank order: 7-position greater than 5-position greater than 6-position. Chromones that contained a 2-substituent that was not coplanar with the chromone ring system showed improved binding over compounds with coplanar substituents. The most potent compound at the sigma site, 7-[[7-(4-hydroxypiperidyl)heptyl]oxy]-2-phenylchromone (74), had receptor affinities (IC50) of 16 nM at the [3H]DTG site, 19 nM at the [3H]-(+)-3-PPP site, and 4000 nM (Ki) at the dopamine D2 receptor. The most selective compound examined, 6-[[6-(4-hydroxypiperidyl)hexyl]-oxy]-2-cyclopentylchromone (58), exhibited IC50s of 51 nM at the [3H]DTG site, 55 nM at the [3H]-(+)-3-PPP site, and 21,000 nM (Ki) at the dopamine D2 receptor. Compound 44 (6-[[6-(4-hydroxypiperidyl)hexyl]oxy]-3-methylflavone, NPC 16377) was systemically effective (ip and po) in two behavioral models predictive of antipsychotic compounds and systemically active in animal models of ischemia.

Chromones↗

Effects of Ca2+ on the kinetics of phosphate release in skeletal muscle.

The process of phosphate dissociation during the muscle cross-bridge cycle has been investigated by photoliberation of inorganic phosphate (Pi) within skinned fibers of rabbit psoas muscle. This permitted a test of the idea that Ca2+ controls muscle contraction by regulating the Pi release step of the cycle. Photoliberation of Pi from structurally distinct "caged" Pi precursors initiated a rapid tension decline of up to 12% of active tension, and this was followed by a slower tension decline. The apparent rate constant of the fast phase, kPi, depended on both [Pi] and [Ca2+], whereas the slow phase generally occurred at 2-4 s-1. At maximal Ca2+, kPi increased in a nonlinear manner from 43 +/- 2 s-1 to 118 +/- 7 s-1, as Pi was raised from 0.9 to 12 mM. This was analyzed in terms of a three-state kinetic model in which a force-generating transition is coupled to Pi dissociation from the cross-bridge. As Ca(2+)-activated tension was reduced from maximal (Pmax) to 0.1 Pmax, (i) kPi decreased by up to 2.5-fold, (ii) the relative amplitude of the rapid phase increased 2-fold, and (iii) the relative amplitude of the slow phase increased about 6-fold. Changes in the rapid phase are compatible with Ca2+ influencing an apparent equilibrium constant for the force-generating transition. By comparison, kPi was faster than the rate constant of tension redevelopment, ktr, and was influenced less by Ca2+. Ca2+ effects on the caged Pi transient cannot account for the large effects of Ca2+ on actomyosin ATPase rates or cross-bridge cycling kinetics but may be a manifestation of reciprocal interactions between the thin filament and force-generating cross-bridges, and may represent Ca2+ regulation of the distribution of cross-bridges between non-force-and force-generating states.

Animals↗