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Biomedical subjects

H M Lu

Publications and source records attributed to H M Lu.

At least 19 recordsLinked to original sources

Comparative biokinetics of tritium in rats during continuous ingestion of tritiated water and tritium-labeled food.

PURPOSE: The biokinetics of tritium during continuous ingestion of tritiated water and tritiated wheat were investigated to estimate the radiation dose rates at the end of two modes of chronic exposure. MATERIALS AND METHODS: Wistar strain male rats continuously ingested tritiated water as drinking water and tritiated wheat as food for 14 weeks. Urine and tissue samples were obtained and total tritium in the fresh wet samples and organically bound tritium (OBT) in the freeze-dried samples were determined. RESULTS: The biokinetics of tritium was different between the two modes of exposure. The concentration of total tritium in the tissues exposed to tritiated water attained a steady-state condition by 2-3 weeks. The steady-state condition in the case of exposure to tritiated wheat was not observed for 10 weeks after the start of exposure in the majority of tissues. The relatively efficient and prolonged OBT formation during chronic exposure to tritiated wheat resulted in relatively high incorporation and retention of tritium in the tissues compared with those for exposure to the same activity of tritiated water. CONCLUSION: Radiation dose rates estimated at the end of continuous ingestion showed that tritiated wheat gave higher dose rates than tritiated water by a factor of 1.3 to 4.5, but the factors were within 2.0 in the majority of tissues except for small intestine and adipose tissue.

Administration, Oral↗

Expression changes of activin A in the development of hepatic fibrosis.

AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enhanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 +/- 0.094 vs 0.2860.0670, P< 0.01; 0.620 +/- 0.134 vs 0.286 +/- 0670, P< 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.

Activins↗

Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study.

PURPOSE: A previous study of healthy female volunteers suggested that deep inspiratory breath holding can reduce the cardiac volume in the treatment portals for left-breast cancer treatment. The reduction of irradiated cardiac volume may be important considering the reported late cardiac morbidity and mortality and the frequent coexistent use of potentially cardiotoxic chemotherapy in breast cancer patients. In the present study, we evaluated the heart volume in the fields and, thus, the true benefit of this respiratory maneuver in breast cancer patients undergoing CT simulation. MATERIALS AND METHODS: Fifteen patients (median age, 53) were studied. For each patient, CT scans were performed both when the patient breathed normally (quiet respiration) and when the patient held her breath after a deep inspiration. Tangential fields were planned using the same medial, lateral, superior, and inferior borders on skin for the normal breathing and the breath-holding configurations. The cardiac and left-lung volumes within the tangential fields were calculated for both breathing configurations. Multiple scan series were performed for the breath-holding configuration to provide a more accurate delineation of the cardiac tissue and to study the reproducibility of the patient's position between different cycles of deep inspiration. RESULTS: None of the patients had difficulty holding her breath for 20 s. The cardiac volume in the field was reduced (-86 +/- 24%; p < 0.001) when patients held their breath after a deep inspiration compared to when breathing normally. For 7 patients (47%), deep inspiration moved the heart completely out of the radiation fields. The expansion of the lung tissue due to deep inspiration also increased the absolute lung volume in the tangential fields (183 cm(3) vs 97 cm(3), p < 0.001). However, the fractional volume of the left lung in the field was essentially unchanged. For all but 1 patient, the maximum difference between the external body contours from different breath holding cycles was 5 mm and occurred at the lateral aspect of the breast. At the medial aspect, as indicated by the position of the midline marker, the variations were well within the currently accepted tolerance for patient positioning during tangential treatment. CONCLUSIONS: Deep-inspiration breath holding substantially reduces cardiac volume in the tangential fields for left-sided breast cancer treatment. The variation between patient positions at different cycles of breath holding was found to be reasonably small. Therefore, it appears feasible to reduce cardiac radiation by treating patients with intratreatment minifractions lasting 10-15 s while patients hold their breath.

Aged↗

Virtual light field projection for CT-simulation.

We report a method to project a virtual light field over the patient during CT-simulations of external beam radiotherapy. It can be used to perform all the tasks associated with the physical light field of a conventional simulator. The system consists of a three-dimensional sonic digitizer interfacing with a window-based software on a personal computer. The digitizer can provide the three-dimensional coordinates of any point in space accessible by the digitizer probe. When these coordinates are transformed into the beam's eye view, the position of the digitized point relative to the beam can readily be displayed. Thus, the system establishes a virtual light field in space, which can be "seen" only by the digitizer probe. For any digitized point, the system can immediately show, by the beam's eye view display, whether the point is inside the field, outside of the field, or on the field border. Moreover, this virtual field projection allows one to evaluate external target coverage (or external normal tissue sparing) conveniently and interactively. By simply digitizing the concerned area and viewing its position in the beam's eye view display, one can immediately assess the coverage and if necessary, modify the treatment field accordingly. The system also provides an efficient and essential procedure in CT-simulations for marking treatment portals on the patient. By cruising the digitizer probe on the patient's skin surface under visual and audio guidances, one can promptly find the projection of the field center, field corners, etc., on the patient. Measurements have been performed to study the accuracy of the GP-12 sonic digitizer using rigid phantoms. Based on the measured data, the overall accuracy of the portal localization system is estimated to be +/-2 mm. The system has been in clinical use for our CT simulator.

Calibration↗

Circadian and septadian variation in the occurrence of acute myocardial infarction in a Chinese population.

To investigate whether circadian or any other temporal pattern(s) exist in the occurrence of acute myocardial infarction (AMI) in a Chinese population, we analyzed 428 patients with confirmed AMI for temporal patterns of AMI occurrence. The patients admitted to the Affiliated Hospital of Shandong Medical University during 1991-95 were from Jinan, the capital city of Shandong Province of China, which has a population of 2.5 million. The chi-square test for goodness of fit was used to test the difference among the frequencies of AMI occurrence in 4 equal intervals (01.00-07.00 h, 07.00-13.00 h, 13.00-19.00 h, 19.00-01.00 h) during the day and among those on 7 days during the week. The results showed that AMI occurrence exhibited significant circadian (p<0.001) and septadian (day of the week) (p=0.046) periodicity, with a peak at 01.00-07.00 h and a trough at 13.00-19.00 h during the day, and a peak on Saturday and a trough on Wednesday during the week. The peak to trough ratio of risk was 2.7 during the day and 2.1 during the week. It is concluded that there were circadian and septadian biorhythms in AMI occurrence in the Chinese population and that these were different from those observed in Western populations. Further investigation of the underlying mechanisms may shed further light on the trigger mechanisms of AMI and thus be helpful in the prevention and treatment of AMI.

Acute Disease↗

Optimized beam planning for linear accelerator-based stereotactic radiosurgery.

PURPOSE: Current treatment planning for linear accelerator-based stereotactic radiosurgery and radiotherapy is a lengthy and iterative procedure. The planner has to manually select the beam arcs and carefully consider many different selections to ensure target volume coverage while sparing dose to critical organs. In this article we report an optimization procedure that can automatically select the beam arcs based on geometric and dosimetric analysis of the treatment parameters. METHODS AND MATERIALS: The optimization problem is introduced by using a Beam's Eye View (BEV) map where a pattern of lines represents a beam arc combination for a treatment plan. The collection of all possible treatment plans is described by using the concept of phase space where each point corresponds to a particular configuration of the system under consideration, and in this case, a particular beam arc combination. A geometric reduction of the phase space is performed by excluding static beam ports that irradiate too much critical organs and too little target volume. The phase space is further reduced by excluding beam arc combinations that do not comply with treatment convenience considerations and established planning experiences. These reductions significantly reduces the number of beam arc combinations to be considered and thus dramatically simplifies the computational complexity. The method of simulated annealing is then used to the reduced phase space to select the set of beam arcs that provides the best surface dose distribution for the target volume. The optimization procedure is applied to a radiosurgery case to compare the optimized beam arcs with the previously manually planned beam arcs. The procedure is also applied to 10 randomly selected cases for a comparison in terms of tissue-volume ratio calculations. RESULTS: The system is a highly automated beam arc planning tool for stereotactic radiosurgery and stereotactic radiotherapy. Its interactive nature allows the planner to rapidly consider many treatment plans to search for the best option. For the case presented, it is shown that the optimized beams substantially reduce the dose to the postrema. The tissue-volume ratio calculations demonstrate that the optimization often produces clinically superior treatment plans than the manual beam planning method. CONCLUSIONS: Our method of phase space reduction proves to be very useful in approaching the complex problem of treatment planning optimization. Not only does it substantially reduce the number of beam arcs that need to be considered, but it also simplifies the evaluation of the beam arc options. Both of these greatly reduce the computational complexity of the optimization and make the procedure fast and efficient. Moreover, the reduction of phase space adds another layer of interaction between the user and the beam selection procedure, so that the optimization process is well controlled and thus very effective.

Brain Neoplasms↗

Interactions of the components of the general secretion pathway: role of Pseudomonas aeruginosa type IV pilin subunits in complex formation and extracellular protein secretion.

The general secretion pathway (GSP), found in a wide range of bacteria, is responsible for extracellular targeting of a subset of proteins from the periplasm. In Pseudomonas aeruginosa, the GSP requires the participation of 12 proteins, of which XcpT, XcpU, XcpV, XcpW are homologues of PilA, the major subunit of type IV pili. The interaction between the pilin-like Xcp proteins was investigated using bifunctional crosslinking reagents. Cross-linking analysis of whole cells of wild-type P. aeruginosa, followed by immunoblot analysis, revealed a 34-kDa XcpT-containing complex. This complex was shown to consist of XcpT/PilA heterodimers. The role of PilA in the GSP was examined, using P. aeruginosa mutants in the pilA gene, or in rpoN, a gene regulating pilA expression. Each mutant showed a significant reduction in the efficiency of extracellular protein secretion, and this defect could be restored by expression of the cloned pilA gene in the mutant cells. The formation of the PilA/XcpT complex did not require XcpR or XcpQ, two other components of the secretion machinery, nor did it require the pilus biogenesis factors PilB and PIlC. The dimeric XcpT/PilA complex was also formed in a pilD mutant, which lacks the leader peptidase enzyme, demonstrating that the leader peptide at the N-terminus or PilA or XcpT did not have to be removed for the dimerization to occur. XcpW and XcpU can also be crosslinked to form dimeric complexes with PilA. When expression of XcpT is increased, its homodimers, as well as XcpT/XcpW heterodimers, can be detected. Finally, an oligohistidine-tagged XcpT was shown to form stoichiometric complexes with PilA, and with XcpT, U, V and W. These dimers were co-purified by nickel-affinity chromatography. The results of this study suggest that XcpT can form heterodimers with PilA, and Xcp U, V and W, which may be assembly intermediates of the secretion apparatus. Alternatively, these may represent dynamic intermediates that facilitate protein secretion by continuous association and dissociation. The requirement for PilA for efficient protein secretion argues for a critical role played by PilA in two related processes during P. aeruginosa infections: formation of an adhesive pilus organelle and secretion of exoenzymes.

Bacterial Outer Membrane Proteins↗

A specific targeting domain in mature exotoxin A is required for its extracellular secretion from Pseudomonas aeruginosa.

A number of Gram-negative bacteria, including Pseudomonas aeruginosa, actively secrete a subset of periplasmic proteins into their surrounding medium. The presence of a putative extracellular targeting signal within one such protein, exotoxin A, was investigated. A series of exotoxin A truncates, fused to beta-lactamase, was constructed. Hybrid proteins, which carry at their N- termini 120, 255, 355 or the entire 613 residues of the mature exotoxin A, were stable and were secreted into the extracellular medium. Hybrid proteins which carry residues 1-30 and 1-60 of the mature exotoxin A were unstable; however, they could be detected entirely within the cells after a short labeling period. A hybrid with beta-lactamase was constructed which carried only the N-terminal residues 1-3 and region 60-120 of exotoxin A. It was also secreted into the culture medium, suggesting that a specific 60 amino acid domain contains the necessary targeting information for translocation of exotoxin A across the outer membrane. The secretion of the hybrid proteins is independent of the passenger protein, since a similar exotoxin A-murine interleukin 4 hybrid protein was also secreted. The extracellular targeting signal between amino acids 60 and 120 is rich in anti-parallel beta-sheets. It has been shown previously to be involved in the interaction of the exotoxin A with the receptors of the eukaryotic cells. In the three- dimensional view, the targeting region is on the toxin surface where it is easily accessible to the components of the extracellular secretion machinery.

ADP Ribose Transferases↗

Clinical evaluation of a rapid immunochromatographic assay based on the 38 kDa antigen of Mycobacterium tuberculosis on patients with pulmonary tuberculosis in China.

SETTING: A rapid membrane-based antibody assay capable of diagnosing pulmonary tuberculosis within 15 min has been developed using the 38 kDa antigen from Mycobacterium tuberculosis. OBJECTIVE: To determine the specificity and sensitivity of this assay and evaluate its usefulness in a clinical setting. DESIGN: Sera from patients with active pulmonary tuberculosis were obtained from three hospitals in China. The control groups consisted of patients who were diagnosed with lung diseases other than tuberculosis and healthy subjects. RESULTS: Antibody was detected in 54 of 61 (89%) sputum positive patients and 67 of 91 (74%) sputum negative patients who had been clinically diagnosed as having active pulmonary tuberculosis. Five out of 56 (9%) patients with respiratory diseases other than tuberculosis and 1 out of 30 (3%) healthy controls had a positive antibody response. The overall specificity of the assay was 93% and the positive predictive value was 95%. We conclude that this assay is rapid, sensitive and specific and will be a valuable aid in the clinical diagnosis of pulmonary tuberculosis.

Adult↗

Effects of egtazic acid and calcimycin on synthesis of DNA and collagen in cultured human lung fibroblasts.

AIM: To study the effects of egtazic acid (EA) and calcimycin (Cal) on the synthesis of DNA and collagen in cultured human lung fibroblasts (HLF). METHODS: The synthesis of DNA and collagen was determined by measuring the incorporation of [3H]TdR and [3H]proline of HLF respectively. RESULTS: The collagen synthesis increased markedly 24 h after exposure to both EA (0.05-4 mmol.L-1) and Cal (0.25-20 mumol.L-1), and that there was no obvious change in DNA synthesis. After 36-48-h exposure, both DNA and collagen syntheses decreased in the groups of EA (1, 2, and 4 mmol.L-1); the DNA synthesis was also suppressed in Cal groups in a concentration-dependent manner, whereas collagen synthesis decreased only in Cal (10 and 20 mumol.L-1). CONCLUSION: Extracellular Ca2+ influx into fibroblasts increased collagen production, However, the DNA synthesis was suppressed when the cytosolic Ca2+ was too high or too low.

Biological Transport, Active↗

Effects of tetrandrine and chlorpromazine on synthesis of collagen and hyaluronic acid in cultured human lung fibroblasts.

AIM: To study the effects of tetrandrine (Tet) and chlorpromazine (Chl) on synthesis of collagen and hyaluronic acid (HA) in cultured human lung fibroblasts (HLF). METHODS: The synthesis of collagen and HA was assessed by measuring the incorporation of [3H]proline and radioimmunoassay. RESULTS: Both Tet (5-80 mumol L-1) and Chl (10-40 mumol L-1) diminished the collagen synthesis in a concentration-dependent manner. The suppression was aggravated at 36-48 h. The HA content in the supernatant of culture also decreased gradually with the increasing dosage of Tet or Chl after 24-h exposure. There was no obvious toxic effect of Tet on HLF cells at 5-20 mumol L-1. CONCLUSION: Tet 5-20 mumol L-1 decreased the production of collagen and HA without obvious toxity on HLF, suggesting that Tet could be a hopeful anti-fibrosis drug.

Alkaloids↗

[The effect of calmodulin antagonist on the anticancer effect of vinblastine].

Calmodulin exists in all eukaryotic cells. It functions as the intracellular receptor of Ca, regulates various cellular physiological processes. We studied the effect of calmodulin antagonist W-7 on the anti-cancer effects of vinblastine. With the method that calmodulin can activate cyclic nucleotide PDE, we found that W-7 can significantly reduce the calmodulin level of MGC803 cell (P < 0.05). W-7 could not only increase the uptaking and accumulating of -3H-Vinblastine in MGC803 cells (P < 0.05), but also decrease the IC50 of Vinblastine (from 12.0 +/- 0.03 nmol to 5.27 +/- 0.02 nmol) in MGC803 cells. It is indicated that calmodulin antagonist W-7 can enhance the anticancer effect of vinblastine.

Adenocarcinoma↗

A periplasmic intermediate in the extracellular secretion pathway of Pseudomonas aeruginosa exotoxin A.

Pseudomonas aeruginosa exotoxin A is synthesized with a secretion signal peptide typical of proteins whose final destination is the periplasm. However, exotoxin A is released from the cell without a detectable periplasmic pool, suggesting that additional determinants in this protein are important for recognition by a specialized machinery of extracellular secretion. The role of the N terminus of the mature exotoxin A in this recognition was investigated. A series of exotoxin A proteins with amino acid substitutions for the glutamic acid pair at the +2 and +3 positions were constructed by mutagenesis of the exotoxin A gene. These N-terminal acidic residues of the mature exotoxin A protein were found to be important not only for efficient processing of the precursor protein but also for extracellular localization of the toxin. The mutated exotoxin A proteins, in which a glutamic acid at the +2 position was replaced by a lysine or a double substitution of lysine and glutamine for the pair of adjacent glutamic acids, accumulated in precursor forms in the mixed cytoplasmic and membrane fractions, which was not seen with the wild-type exotoxin A. The processing of the precursor form of one exotoxin A mutant, in which the glutamic acid at the +2 position was replaced with a glutamine, was not affected. Moreover, a substantial fraction of the mature forms of all three mutants of exotoxin A accumulated in the periplasm, while wild-type exotoxin A could be detected only extracellularly. The periplasmic pools of these variants of exotoxin A could therefore represent the intermediate state during extracellular secretion. The signal for extracellular localization may be located in a small region near the amino terminus of the mature protein or could consist of several regions that are brought together after the polypeptide has folded. Alternatively, the acidic residues may be important for ensuring a conformation essential for exotoxin A to traverse the outer membrane.

ADP Ribose Transferases↗

Distribution of materno-fetus materno-suckling transfer of tritium after single injection of tritiated water in mice.

The metabolism and transfer of tritium from pregnant mice to fetus after injection of tritiated water intraperitoneally was investigated in this paper. The study was composed of three experiments. 1. Pregnant mice were injected with tritium water on the first day of pregnancy, in order to obtain a transfer coefficient of tritium from pregnant mice to fetus through placenta. 2. Pregnant mice were injected with tritiated water on the first day of parturition to study the transfer of tritium via mother milk from nursing mice to the baby-animals. 3. Pregnant mice were injected with tritiated water in different periods of gestation. The results showed that tritiated water was uniformly distributed in all of the tissues measured, including placenta, fetal membrane and amniotic fluid in experiment 1. No effect of placentas on tritium transfer from pregnant mice to fetus was found. Concentration of tritium in the baby's tissues was evidently higher than that in the pregnant mice in experiments 2 and 3, and the transfer coefficient in experiments 2 and 3 was generally higher than that in experiment 1.

Animals↗

Biokinetics of tritium incorporation into the tissues of rats during continuous ingestion of tritiated water or tritium-labeled food.

Wistar strain male rats were continuously given tritiated water or tritiated wheat as drinking water or food for 70 days. During the ingestion, the tritium incorporation into rat tissues was examined in both wet and dry samples of liver, kidney, testis and blood. The concentration of organically bound tritium (OBT) in dry tissues of rats exposed to tritiated water (HTO) and 3H-food (tritiated wheat) attained an equilibrium within 2-3 weeks after the exposure. The concentration of OBT in dry tissues of rats exposed to HTO also reached an equilibrium within 3-4 weeks after the exposure. However, rats exposed to 3H-food, except for the liver, such an equilibrium state was not reached in other tissues and the OBT concentrations increased gradually throughout the exposure. The relative concentrations of total 3H and OBT at the end of the chronic ingestion of 3H food (70 day), expressed in percentages of the total activity were 1 and 9 times higher than those in rats exposed to HTO, respectively. In both groups, OBT as well as total 3H was almost uniformly distributed among the tissues examined.

Animals↗

A proline residue near the amino terminus of the mature domain of secretory proteins lowers the level of the proton motive force required for translocation.

A large variety of proOmpF-Lpps, hybrid secretory proteins composed of the signal region of proOmpF and the mature part of the major lipoprotein, either possessing or not possessing a proline residue near the amino terminus of their mature domains, were constructed at a DNA level, and the rates of their in vitro translocation were determined in the presence and absence of the proton motive force (delta muH+). A proline residue at the signal peptide cleavage site (position +1) blocked the cleavage reaction but not the translocation reaction. All the proOmpF-Lpps examined exhibited approximately the same translocation rate in the presence of delta muH+ irrespective of the presence or absence of a proline residue near the amino terminus. In the absence of the delta muH+, which was achieved by either depletion of the respiratory substrate or the use of urea-treated membrane vesicles permeable to protons, proOmpF-Lpps possessing a proline residue near the amino terminus of the mature domain were translocated whereas those possessing no proline residue in this region were not translocated at all or only very weakly. The position of the proline residue was then moved stepwise away from the amino terminus of the mature domain. The further the position was moved away, the slower was the rate of translocation in the absence of delta muH+. The removal of the proline residue at position +2 of the mature domain of proOmpA also made the delta mu(H+)-independent translocation appreciably slower. It is suggested that the conformational flexibility endowed by the proline residue on the junction region between the signal peptide and the mature domain allows the translocation in the absence of delta muH+ and that this junction region must take on a particular conformation for initiation of the translocation reaction.

Amino Acid Sequence↗

[Significance of serum procollagen-III-peptide in reflecting the therapeutic effects of calcium-channel blockers on hepatic fibrosis].

Changes in serum procollagen-III-peptide (PIIIP) and intravenous tryptophan tolerance test (ITT) were studied in 121 patients with liver cirrhosis during a follow-up period of up to 18 months. The patients received either nifedipine (31 cases, 60 mg/day), verapamil (28 cases, 120 mg/day), cinnarizine (29 cases, 150 mg/day) or tetrandrine (33 cases, 150 mg/day). The significant changes were found in ITT in any of the four drugs administrated for over three months. Serum PIIIP concentration decreased significantly in patients under tetrandrine therapy for 18 months (12.06 +/- 3.91 ng/ml vs 16.57 +/- 5.69 ng/ml before treatment). These data suggest that tetrandrine therapy may have favourable effects on hepatic fibrosis and improvement of liver function in liver cirrhosis.

Adult↗