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Biomedical subjects

H M Lu

Publications and source records attributed to H M Lu.

30 records · Page 2Linked to original sources

[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↗

Intravenous tryptophan tolerance test for liver function.

An intravenous tryptophan tolerance test (ITrpTT) was designed for liver function since 95% Trp is metabolized by the liver. After an intravenous loading dose of 4 mg/kg body weight, serum levels of both free (F) and total (T) Trp were determined at 45 and 60 minutes. In normal controls and nonhepatic-disease patients, F45 (60) and T45 (60) did not exceed 7 mumol/L and 80 mumol/L, respectively, and F/T ratio not greater than 0.14. These were set up as cutoffs of upper normal limits. The test was abnormal in 87.5% of chronic persistent hepatitis (CPH) characterized by elevation of T45 (60), 100% of chronic active hepatitis (CAH) by elevation of F45 (60) and/or T45 (60), and 100% of hepatic cirrhosis by increase in F45 (60) and F/T ratio but not in T45 (60). The test seems to be more sensitive than the conventional tests for liver function. However, one should be cautious in interpretation of the test as there are some factors which might influence the Trp metabolism like exercise, alcoholism, corticosteroids and enzyme-inducers. It merits as an indication of liver dysfunction only when these factors are considered and excluded.

Adult↗

The significance of 5'-nucleotide phosphodiesterase isozymes in the diagnosis of liver carcinoma.

The results of determination of the serum 5'-NPDase isozymes in 95 cases of primary liver carcinoma and other kinds of disease are presented. The 5'-NPDase-V was positive in 83.2% of primary liver cancer cases. This test might be a useful supplement to AFP determination, especially in AFP-negative liver cancer patients. In most patients who had undergone successful liver resection for primary carcinoma, the test became negative. A positive 5'NPDase-V test in patients with cancer elsewhere in the body may suggest liver metastasis. In addition, this test may be of some help in the differentiation of primary liver cancer from other kinds of liver disease. The problem of "false-positive" results of this test is discussed.

Diagnosis, Differential↗