Three-dimensional superlattices built from (M(4)In(16)S(33))(10-)(M = Mn, Co, Zn, Cd) supertetrahedral clusters.
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Journal Article↗
Biomedical subjects
N Zheng
Publications and source records attributed to N Zheng.
Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation.
We analyzed the der(11) and der(4) genomic breakpoint junctions of a t(4;11) in the leukemia of a patient previously administered etoposide and dactinomycin by molecular and biochemical approaches to gain insights about the translocation mechanism and the relevant drug exposure. The genomic breakpoint junctions were amplified by PCR. Cleavage of DNA substrates containing the normal homologues of the MLL and AF-4 translocation breakpoints was examined in vitro upon incubation with human DNA topoisomerase IIalpha and etoposide, etoposide catechol, etoposide quinone, or dactinomycin. The der(11) and der(4) genomic breakpoint junctions both involved MLL intron 6 and AF-4 intron 3. Recombination was precise at the sequence level except for the overall gain of a single templated nucleotide. The translocation breakpoints in MLL and AF-4 were DNA topoisomerase II cleavage sites. Etoposide and its metabolites, but not dactinomycin, enhanced cleavage at these sites. Assuming that DNA topoisomerase II was the mediator of the breakage, processing of the staggered nicks induced by DNA topoisomerase II, including exonucleolytic deletion and template-directed polymerization, would have been required before ligation of the ends to generate the observed genomic breakpoint junctions. These data are inconsistent with a translocation mechanism involving interchromosomal recombination by simple exchange of DNA topoisomerase II subunits and DNA-strand transfer; however, consistent with reciprocal DNA topoisomerase II cleavage events in MLL and AF-4 in which both breaks became stable, the DNA ends were processed and underwent ligation. Etoposide and/or its metabolites, but not dactinomycin, likely were the relevant exposures in this patient.
Antigens, Neoplasm↗
The cost of exposing a hydrophobic loop and implications for the functional role of 4.5 S RNA in the Escherichia coli signal recognition particle.
The signal recognition particle (SRP) is an RNA-protein complex that directs ribosomes to the rough endoplasmic reticulum membrane by binding to targeting signals found on the nascent chain of proteins destined for export to the endoplasmic reticulum. We found evidence from studies with fragments of the protein component of the Escherichia coli SRP that a long hydrophobic loop (the so-called "finger loop") is detrimental to the stability of its signal peptide-binding domain, the M domain. This hydrophobic loop is highly conserved and thus may have a critical role in the function of the SRP. Given our previously reported evidence that 4.5 S RNA stabilizes the tertiary fold of the M domain (Zheng, N., and Gierasch, L. M. (1997) Mol. Cell 1, 79-87), we now propose that the functional requirement for 4.5 S RNA resides in its ability to counteract the destabilizing influence of the finger loop.
Amino Acid Sequence↗
Simultaneous determination of etoposide and its catechol metabolite in the plasma of pediatric patients by liquid chromatography/tandem mass spectrometry.
The anticancer drug etoposide is associated with leukemias with MLL gene translocations and other translocations as a treatment complication. The genotype of cytochrome P450 3A4 (CYP3A4), which converts etoposide to its catechol metabolite, influences the risk. In order to perform pharmacokinetic studies aimed at further elucidation of the translocation mechanism, we have developed and validated a liquid chromatography/electrospray/tandem mass spectrometry assay for the simultaneous analysis of etoposide and its catechol metabolite in human plasma. The etoposide analog teniposide was used as the internal standard. Liquid chromatography was performed on a YMC ODS-AQ column. Simultaneous determination of etoposide and its catechol metabolite was achieved using a small volume of plasma, so that the method is suitable for pediatric patients. The limits of detection were 200 ng ml(-1) etoposide and 10 ng ml(-1) catechol metabolite in human plasma and 25 ng ml(-1) etoposide and 2.5 ng ml(-1) catechol metabolite in protein-free plasma, respectively. Acceptable precision and accuracy were obtained for concentrations in the calibration curve ranges 0.2--100 microg ml(-1) etoposide and 10--5000 ng ml(-1) catechol metabolite in human plasma. Acceptable precision and accuracy for protein-free human plasma in the range 25--15 000 ng ml(-1) etoposide and 2.5--1500 ng ml(-1) etoposide catechol were also achieved. This method was selective and sensitive enough for the simultaneous quantitation of etoposide and its catechol as a total and protein-free fraction in small plasma volumes from pediatric cancer patients receiving etoposide chemotherapy. A pharmacokinetic model has been developed for future studies in large populations.
Antineoplastic Agents, Phytogenic↗
Kinematic comparisons of 1996 Olympic baseball pitchers.
The aim of this study was to compare and evaluate the kinematics of baseball pitchers who participated in the 1996 XXVI Centennial Olympic Games. Two synchronized video cameras operating at 120 Hz were used to video 48 pitchers from Australia, Japan, the Netherlands, Cuba, Italy, Korea, Nicaragua and the USA. All pitchers were analysed while throwing the fastball pitch. Twenty-one kinematic parameters were measured at lead foot contact, during the arm cocking and arm acceleration phases, and at the instant of ball release. These parameters included stride length, foot angle and foot placement; shoulder abduction, shoulder horizontal adduction and shoulder external rotation; knee and elbow flexion; upper torso, shoulder internal rotation and elbow extension angular velocities; forward and lateral trunk tilt; and ball speed. A one-way analysis of variance (P < 0.01) was used to assess kinematic differences. Shoulder horizontal adduction and shoulder external rotation at lead foot contact and ball speed at the instant of ball release were significantly different among countries. The greater shoulder horizontal abduction observed in Cuban pitchers at lead foot contact is thought to be an important factor in the generation of force throughout the arm cocking and arm acceleration phases, and may in part explain why Cuban pitchers generated the greatest ball release speed. We conclude that pitching kinematics are similar among baseball pitchers from different countries.
Acceleration↗
Effects of technique variations on knee biomechanics during the squat and leg press.
PURPOSE: The specific aim of this project was to quantify knee forces and muscle activity while performing squat and leg press exercises with technique variations. METHODS: Ten experienced male lifters performed the squat, a high foot placement leg press (LPH), and a low foot placement leg press (LPL) employing a wide stance (WS), narrow stance (NS), and two foot angle positions (feet straight and feet turned out 30 degrees ). RESULTS: No differences were found in muscle activity or knee forces between foot angle variations. The squat generated greater quadriceps and hamstrings activity than the LPH and LPL, the WS-LPH generated greater hamstrings activity than the NS-LPH, whereas the NS squat produced greater gastrocnemius activity than the WS squat. No ACL forces were produced for any exercise variation. Tibiofemoral (TF) compressive forces, PCL tensile forces, and patellofemoral (PF) compressive forces were generally greater in the squat than the LPH and LPL, and there were no differences in knee forces between the LPH and LPL. For all exercises, the WS generated greater PCL tensile forces than the NS, the NS produced greater TF and PF compressive forces than the WS during the LPH and LPL, whereas the WS generated greater TF and PF compressive forces than the NS during the squat. For all exercises, muscle activity and knee forces were generally greater in the knee extending phase than the knee flexing phase. CONCLUSIONS: The greater muscle activity and knee forces in the squat compared with the LPL and LPH implies the squat may be more effective in muscle development but should be used cautiously in those with PCL and PF disorders, especially at greater knee flexion angles. Because all forces increased with knee flexion, training within the functional 0-50 degrees range may be efficacious for those whose goal is to minimize knee forces. The lack of ACL forces implies that all exercises may be effective during ACL rehabilitation.
Adult↗
[Study of the cytotoxity against human hepatocellular carcinoma cells induced by the MAGE-1 gene modified dendritic cells].
OBJECTIVE: To genetically modify dendritic cells (DC) with a tumor associated antigen gene MAGE-1 and to observe in vitro the cytotoxic effect induced by this genetically modified DC against human hepatocellular carcinoma (HCC) cell line SMMC7721, thus giving a primary verification of the possibility of this genetically modified DC to induce specific antitumor immunity against HCC and serving as a new type of vaccine. METHODS: The MAGE-1 gene was inserted into the retrovirus vector LXSN to construct the recombinant retrovirus LMSN. The monocyte-derived DCs were transfected by LMSN and control virus LXSN respectively as well as a third group was set up as non-transfected control. The MAGE-1 gene expression in LMSN transfected DC was identified by Western blot and the in vitro cytotoxities against SMMC7721 induced by three groups of DC were tested by MTT assay. RESULTS: A recombinant retrovirus LMSN containing the tumor rejection antigen gene MAGE-1 was successfully constructed and the MAGE-1 gene expression in LMSN transfected human monocyte-derived DC was induced. The LMSN transfected DC could induce very high lytic activity against SMMC7721 in vitro with the lytic activity of 78.9%+/-3.6%. Nevertheless, the LXSN transfected DC and non-transfected DC only induced relatively lower lytic activity as 34.7%+/-4.3% and 3.9%+/-2.0%, respectively. The difference of the lytic activities between those three groups as statistically significant (P<0.01). CONCLUSIONS: The MAGE-1 gene transfected DC can induce higher in vitro cytotoxicity against SMMC7721, suggesting the possibility of this genetically modified DC to induce specific antitumor activity and to serve as a new type of vaccine for HCC.
Animals↗
Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases.
Ubiquitin-protein ligases (E3s) regulate diverse cellular processes by mediating protein ubiquitination. The c-Cbl proto-oncogene is a RING family E3 that recognizes activated receptor tyrosine kinases, promotes their ubiquitination by a ubiquitin-conjugating enzyme (E2) and terminates signaling. The crystal structure of c-Cbl bound to a cognate E2 and a kinase peptide shows how the RING domain recruits the E2. A comparison with a HECT family E3-E2 complex indicates that a common E2 motif is recognized by the two E3 families. The structure reveals a rigid coupling between the peptide binding and the E2 binding domains and a conserved surface channel leading from the peptide to the E2 active site, suggesting that RING E3s may function as scaffolds that position the substrate and the E2 optimally for ubiquitin transfer.
Amino Acid Sequence↗
Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy.
To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction on small pools of DNA equivalent to 100 sperm and Southern blotting were used to screen at least 7900 sperm in each sample to quantify the mutation frequency at the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were obtained at least 2 months after completion of therapy from 4 patients treated with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that lacks alkylating agents and from three patients treated with regimens (Cytoxan, vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine, lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine and prednisone [MOPP]) containing alkylating agents. There were no effects of NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there was a statistically significant increase in mutation frequency from 0.79% pretreatment to 1.14% posttreatment, indicating induction of mutations in stem spermatogonia. During-treatment semen samples obtained from 2 patients treated with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP also did not show any increases above the baseline mutation frequencies, indicating no increase in the minisatellite mutation frequency in spermatocytes. Thus, measurement of repeat number changes at minisatellite MS205 appears to be able to detect induced germline mutations in human sperm. However, most chemotherapy regimens do not significantly increase this class of mutations.
Adult↗
Novel Single- and Double-Layer and Three-Dimensional Structures of Rare-Earth Metal Coordination Polymers: The Effect of Lanthanide Contraction and Acidity Control in Crystal Structure Formation.
Lanthanide atom sizes (the lanthanide contraction) directly control the type of structure formed by the coordination of a single multidentate ligand, 3,5-pyrazoledicarboxylic acid (H(3)pdc). Single-layer, double-layer ([Eu(2)(Hpdc)(3)(H(2)O)(6)], see picture), and three-dimensional networks were found. Control of the reaction pH plays a key role in the structure formation in this system.
Journal Article↗
Biomechanics and motion analysis applied to sports.
The development of motion analysis and the application of biomechanical analysis techniques to sports has paralleled the exponential growth of computational and videographic technology. Technological developments have provided for advances in the investigation of the human body and the action of the human body during sports believed to be unobtainable a few years ago. Technological advancements have brought biomechanical applications into a wide range of fields from orthopedics to entertainment. An area that has made tremendous gains using biomechanics is sports science. Coaches, therapists, and physicians are using biomechanics to improve performance, rehabilitation, and the prevention of sports related injuries. Functional analyses of athletic movements that were impossible a few years ago are available and used today. With new advancements, the possibilities for investigating the way a human interacts and reacts to environmental conditions are ever expanding.
Athletic Injuries↗
[Pharmacokinetic study on absorption of stachyose].
OBJECTIVE: To study the intestinal absorption and absorption site of stachyose, one of the oligosaccharides extracted from Rehmannia, in mice and rats. METHODS: Plasma concentration of stachyose was measured by high performance liquid chromatography (HPLC) with postcolumn fluorescence derivatization after administration of stachyose to mice by oral or intravenous injection. The absorption of stachyose in different sections of digestive tract was evaluated using the intestine loop in situ technique. The kanamycin treated mice were used to study the metabolism of stachyose in intestine. RESULTS: Absorption of stachyose in intestine after oral administration was quick but low, the bioavailability being 3.82%. The absorption rate in stomach, duodenum, jejunum and ileum was 6.03%, 13.80%, 8.33% and 0.53% respectively, no absorption was tested in large intestine. The residual rate of stachyose in the intestine of normal mice and kanamycin treated mice was 8.6% and 93.4% respectively. CONCLUSION: The intestinal absorption rate of stachyose is low, the main absorption site is the upper portion of small intestine. The unabsorbed stachyose is metabolized by the intestinal microflora.
Animals↗
Isolation of HIV type 1 from long-term nonprogressors in Herpesvirus saimiri-immortalized T cells.
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Cell Line, Transformed↗
Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP.
The E2F and DP protein families form heterodimeric transcription factors that play a central role in the expression of cell cycle-regulated genes. The crystal structure of an E2F4-DP2-DNA complex shows that the DNA-binding domains of the E2F and DP proteins both have a fold related to the winged-helix DNA-binding motif. Recognition of the central c/gGCGCg/c sequence of the consensus DNA-binding site is symmetric, and amino acids that contact these bases are conserved among all known E2F and DP proteins. The asymmetry in the extended binding site TTTc/gGCGCc/g is associated with an amino-terminal extension of E2F4, in which an arginine binds in the minor groove near the TTT stretch. This arginine is invariant among E2Fs but not present in DPs. E2F4 and DP2 interact through an extensive protein-protein interface, and structural features of this interface suggest it contributes to the preference for heterodimers over homodimers in DNA binding.
Amino Acid Sequence↗
Kinematic and kinetic comparison of baseball pitching among various levels of development.
Proper biomechanics help baseball pitchers minimize their risk of injury and maximize performance. However previous studies involved adult pitchers only. In this study, 23 youth, 33 high school, 115 college, and 60 professional baseball pitchers were analyzed. Sixteen kinematic (11 position and five velocity), eight kinetic, and six temporal parameters were calculated and compared among the four levels of competition. Only one of the 11 kinematic position parameters showed significant differences among the four levels, while all five velocity parameters showed significant differences. All eight kinetic parameters increased significantly with competition level. None of the six temporal parameters showed significant differences. Since 16 of the 17 position and temporal parameters showed no significant differences, this study supports the philosophy that a child should be taught 'proper' pitching mechanics for use throughout a career. Kinetic differences observed suggest greater injury risk at higher competition levels. Since adult pitchers did not demonstrate different position or temporal patterns than younger pitchers, increases in joint forces and torques were most likely due to increased strength and muscle mass in the higher level athlete. The greater shoulder and elbow angular velocities produced by high-level pitchers were most likely due to the greater torques they generated during the arm cocking and acceleration phases. The combination of more arm angular velocity and a longer arm resulted in greater linear ball velocity for the higher level pitcher. Thus, it appears that the natural progression for successful pitching is to learn proper mechanics as early as possible, and build strength as the body matures.
Adolescent↗
An analytical model of the knee for estimation of internal forces during exercise.
An analytical model of the knee joint was developed to estimate the forces at the knee during exercise. Muscle forces were estimated based upon electromyographic activities during exercise and during maximum voluntary isometric contraction (MVIC), physiological cross-sectional area (PCSA), muscle fiber length at contraction and the maximum force produced by an unit PCSA under MVIC. Tibiofemoral compressive force and cruciate ligaments' tension were determined by using resultant force and torque at the knee, muscle forces, and orientations and moment arms of the muscles and ligaments. An optimization program was used to minimize the errors caused by the estimation of the muscle forces. The model was used in a ten-subject study of open kinetic chain exercise (seated knee extension) and closed kinetic chain exercises (leg press and squat). Results calculated with this model were compared to those from a previous study which did not consider muscle length and optimization. Peak tibiofemoral compressive forces were 3134 +/- 1040 N during squat, 3155 +/- 755 N during leg press and 3285 +/- 1927 N during knee extension. Peak posterior cruciate ligament tensions were 1868 +/- 878 N during squat, 1866 +/- 383 N during leg press and 959 +/- 300 N for seated knee extension. No significant anterior cruciate ligament (ACL) tension was found during leg press and squat. Peak ACL tension was 142 +/- 257 N during seated knee extension. It is demonstrated that the current model provided better estimation of knee forces during exercises, by preventing significant overestimates of tibiofemoral compressive forces and cruciate ligament tensions.
Anterior Cruciate Ligament↗
Biomechanics of the knee during closed kinetic chain and open kinetic chain exercises.
PURPOSE: Although closed (CKCE) and open (OKCE) kinetic chain exercises are used in athletic training and clinical environments, few studies have compared knee joint biomechanics while these exercises are performed dynamically. The purpose of this study was to quantify knee forces and muscle activity in CKCE (squat and leg press) and OKCE (knee extension). METHODS: Ten male subjects performed three repetitions of each exercise at their 12-repetition maximum. Kinematic, kinetic, and electromyographic data were calculated using video cameras (60 Hz), force transducers (960 Hz), and EMG (960 Hz). Mathematical muscle modeling and optimization techniques were employed to estimate internal muscle forces. RESULTS: Overall, the squat generated approximately twice as much hamstring activity as the leg press and knee extensions. Quadriceps muscle activity was greatest in CKCE when the knee was near full flexion and in OKCE when the knee was near full extension. OKCE produced more rectus femoris activity while CKCE produced more vasti muscle activity. Tibiofemoral compressive force was greatest in CKCE near full flexion and in OKCE near full extension. Peak tension in the posterior cruciate ligament was approximately twice as great in CKCE, and increased with knee flexion. Tension in the anterior cruciate ligament was present only in OKCE, and occurred near full extension. Patellofemoral compressive force was greatest in CKCE near full flexion and in the mid-range of the knee extending phase in OKCE. CONCLUSION: An understanding of these results can help in choosing appropriate exercises for rehabilitation and training.
Adult↗
Biomechanical modelling of the human sacroiliac joint.
From a mechanical point of view, the human pelvis can be considered as a stable, complex three link structure. This three-link closed-chain system explains why there is so little motion in the sacroiliac joint. Based on the minimum total potential energy principle, a quasi-static model of the human pelvis with its three joints is developed. In the model, the articular cartilage linings of the joint surfaces are considered as thin layers with a geometric non-linear behaviour. They lie between two rigid curved surfaces that are represented by small three-node elements. Accessory ligaments and capsules are represented by a number of non-linear springs. A primary model is developed based on a female cadaver. According to the primary model, the translation of the sacroiliac joint in the direction of force is about 0.5 mm in the lateral direction, about 1.8 mm in the antero-posterior direction, and about 1.5 mm in the superior or inferior direction, when a load of 1000 N is applied to the sacrum. When a load of 50 N m-1 is applied to the sacrum, the rotation in the load direction is about 1.6 degrees in axial rotation, about 1.0 degree in flexion or extension and about 1.1 degrees in lateral bending.
Biomechanical Phenomena↗