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Biomedical subjects

J H Li

Publications and source records attributed to J H Li.

At least 91 records · Page 5Linked to original sources
PubMed1997

Intracellular pH and heat sensitivity in two human cancer cell lines.

BACKGROUND AND PURPOSE: The majority of studies which have demonstrated a linear correlation between intracellular pH (pHi) and thermosensitivity have used rodent cell lines. In order to understand the therapeutic potential of this strategy, it is necessary to determine whether similar observations can be obtained with human cancer cells. MATERIALS AND METHODS: Human breast cancer MCF-7, and nasopharyngeal carcinoma CNE-1 cell lines were heated at 43 degrees C under extracellular pH (pHe) conditions of 7.2 or 6.8, +/- NaHCO3. We studied the function of the Na+/H+ antiport, one of the primary membrane regulators of pHi, pHi level, and clonogenic survival after these treatments. RESULTS: After 2-h exposure to 43 degrees C at pHe 7.2, antiport activity in MCF-7 cells was > 50% relative to that of unheated cells, in contrast to < 20% relative activity for CNE-1 cells. Respective survival levels under these conditions were 0.25 and 0.04. The addition of 5-(N-ethyl-N-isoproply) amiloride (EIPA), a potent inhibitor of Na+/H+ antiport, had no effect on MCF-7 cells, but enhanced cytotoxicity for CNE-1 cells, when heated at pHe 6.8 without NaHCO3. Analysis of the correlation between log surviving fraction and pHi demonstrated that this relationship was much steeper for CNE-1 compared to MCF-7 cells. CONCLUSION: The relationship between pHi levels and thermosensitivity observed in rodent cells can also apply to two human cancer cell lines: MCF-7 and CNE-1, with the latter cells being apparently more amenable to manipulations of pHi regulation compared to the former.

Amiloride↗
PubMed1997

[Estimating concentrations of serum total digoxin and digoxin-like immunoreactive substances in patients of cardiac failure with renal insufficiency].

Measurement of serum digoxin concentration is recommended as a routine in patients undergoing digoxin therapy because its therapeutic range is narrow. The presence of a high concentration of digoxin-like immunoreactive substances(DLIS) in human serum have been reported in a number of pathophysiological conditions. DLIS which cross-react with anti-digoxin antibodies, can falsely elevate the total digoxin concentration and is troublesome in the therapeutic monitoring of digoxin. The concentrations of serum total digoxin and DLIS in twelve patients of cardiac failure with renal insufficiency were estimated after determination of free digoxin by ultrafiltration with fluorescence polarization immunoassay. In these patients, the free digoxin concentration in serum determined was 0.79 +/- 0.48 (0.46-2.10) nmol.L-1. The total digoxin determined(1.31 +/- 0.80 nmol.L-1) was significantly higher than the calculated total digoxin(1.05 +/- 0.64 nmol.L-1) (P < 0.01), suggesting the presence of elevated DLIS in serum for these patients. The calculated DLIS concentration was 0.27 +/- 0.19(0.07-0.76) nmol.L-1. The results were well consistent with that obtained by recently published method of Dasgupta et al. In conclusion, the approach presented in this paper can estimate the true serum concentrations of digoxin and DLIS in patients of chronic cardiac failure with renal insufficiency.

Cardenolides↗
PubMed1997

Cytotoxic effects of Ad5CMV-p53 expression in two human nasopharyngeal carcinoma cell lines.

Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore novel therapeutic strategies in the management of this disease, the potential of Ad5CMV-p53-mediated gene transfer to NPC cells was investigated in vitro. Two NPC cell lines, CNE-1 and CNE-2Z, were infected with either Ad5CMV-p53 or Ad5CMV-beta-galactosidase and evaluated for transduction efficiency and cytotoxicity. At a multiplicity of infection of 50 plaque-forming units (pfu)/cell, Ad5CMV-beta-galactosidase infection and beta-galactosidase expression were detected in almost 100% of treated NPC cells. High levels of recombinant p53 protein expression were also observed in the NPC cell lines when treated with Ad5CMV-p53 at 50 pfu/cell. Expression of recombinant p53 was dose and time dependent, with peak levels observed at 24 h. A marked increase in WAF1/CIP1 expression was also observed in NPC cells after Ad5CMV-p53 infection. Expression of bcl-2 and bax were minimally detectable at baseline; infection with Ad5CMV-p53 induced no changes in the protein levels in the NPC cells. Growth of NPC cells treated with Ad5CMV-p53 was observed to be significantly inhibited when determined by either the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or clonogenic assay. Infection with Ad5CMV-p53 at 25 pfu/cell resulted in survival levels of 0.35 and 11% in CNE-1 and CNE-2Z cells, respectively. Chromatin condensation and DNA fragmentation were also observed, demonstrating that these cells were undergoing apoptosis. However, when GM38 (normal human fibroblasts) were subjected to identical treatments, they demonstrated significantly lower infection efficiency and transgene expression and were resistant to Ad5CMV-p53-mediated cytotoxicity. These data demonstrate the efficacy of Ad5CMV-p53-mediated gene therapy in human NPC, thus warranting additional investigations of this therapeutic strategy.

Adenoviruses, Human↗
PubMed1996

Modification of mitomycin C-induced clastogenicity by Terminalia catappa L. in vitro and in vivo.

The water extract of the leaves of Terminalia catappa L. was tested for inhibition of mitomycin C-induced micronuclei in CHO-K1 cells. The simultaneous and pre-treatment of CHO-K1 cells with T. catappa extract (75 and 150 micrograms/ml) significantly (P < 0.05) suppressed mitomycin C-induced micronuclei. Furthermore, gastric intubation of T. catappa extract (4.8 and 24 mg/animal per day) to male ICR mice for 8 days significantly (P < 0.01) reduced mitomycin C-induced micronuclei in peripheral blood. In addition, T. catappa dose dependently inhibited lipid peroxidation in vitro and TPA-induced hydrogen peroxide formation in human mononuclear leukocytes. The anticlastogenic effects of T. catappa in vitro and in vivo may be attributed to its antioxidative potential.

Animals↗
PubMed1996

Toxicity of cationic lipid-ribozyme complexes in human prostate tumor cells can mimic ribozyme activity.

Prostate tumor cell lines have been shown to both produce interleukin-6 (IL-6) and express the IL-6 receptor, suggesting a potential autocrine growth regulatory role for IL-6. We explored the role of IL-6 in the proliferation of the human prostatic carcinoma cell line, DU145, using ribozymes to inhibit IL-6 expression. Hammerhead-type ribozymes targeted against IL-6 mRNA sequences were prepared, and in vitro analyses were used to demonstrate that these molecules catalyzed the cleavage of IL-6 mRNA poly- nucleotide fragments. To test in situ activity, these ribozymes were transfected into DU145 cells using cationic transfection lipids, cytofectins. Treatment of cultured cells with ribozyme/cationic lipid complexes resulted in a reduction of IL-6 protein levels in the supernatant and reduced numbers of DU145 cells 48 h after treatment. However, similar results were also seen following treatment with control RNA/lipid complexes. This reduction in IL-6 levels and cell numbers was a function of the RNA/lipid complexes and was not seen with either lipid or RNA alone. Therefore, the reductions in IL-6 levels and cell numbers observed were not due to ribozyme-mediated cleavage of IL-6 mRNA, but rather reflected a dose-dependent, nonspecific toxic effect of the treatment with ribozyme/cytofectin complexes. This effect can resemble functional ribozyme activity, complicating analysis of the activity of synthetic ribozymes after transfection into cultured cells.

Base Sequence↗
PubMed1996

Influence of heat on Na(+)-dependent HCO3-/Cl- exchanger function in a thermoresistant cell line.

During previous studies on the relationship between thermosensitivity and intracellular pH (pHi) regulation in mammalian cells, we observed that the thermoresistant TR-4 cells appeared to be resistant to manipulations of the Na+/H+ antiport, one of the two primary membrane regulators of pHi. We hypothesized that this might be due to up-regulation of the alternate pHi regulator, the Na(+)-dependent HCO3-/Cl- exchanger, in the TR-4 cells. We have now evaluated the effect of heat exposure on the function of the Na(+)-dependent HCO3-/Cl- exchanger in both the parent RIF-1 and the thermoresistant variant TR-4 cells. We also assessed thermosensitivity of the cell lines under conditions of either pHe 7.2 or 6.8, with NaHCO3, with or without the addition of DIDS, an inhibitor of HCO3-/Cl- exchanger function. After 2h of heating at 43 degrees C, relative exchanger function declined to around 50% for the TR-4 cells and 10% for the RIF-1 cells. DIDS (0.2 mM) enhanced thermal cytotoxicity in both cells lines, by around 1 log when the cells were heated at neutral conditions, and by around 1.5 log when the condition became acidic. Results from pHi measurements during heating reflected the clonogenic survival data in that lower pHi levels were associated with the conditions when DIDS was present. We conclude that in the TR-4 cells, the Na(+)-dependent HCO3-/Cl- exchanger appears to be a more important regulator of pHi than the Na+/H+ antiport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Fast EIT data acquisition system with active electrodes and its application to cardiac imaging.

A wide-band high-speed data acquisition system for electrical impedance tomography (EIT) is described. 32 active electrodes are used in the system, half of them as receive electrodes and the other half as drive electrodes. A buffer is mounted on the back of each receive electrode and a current source on each drive electrode. A multielectrode system with active electrodes was built to make it convenient to attach all the electrodes on the human thorax. The system is suitable for both dynamic imaging and multifrequency electrical impedance tomography (MFEIT). Its operating frequency can be chosen between 24 kHz and 400 kHz. Current is injected sequentially into 16 adjacent current electrode pairs and the 16 voltages between adjacent receive electrodes are measured for each current injection. ECG is collected to determine the relationship between the reconstructed images and cardiac activity. The collection of one frame of data is completed within 25 ms. The system has been successfully used for imaging the variation of conductivity distribution of the human thorax. The beat-by-beat cardiac-related change of conductivity distribution has been imaged by our system. The quasi-periodic variation of the impedance distribution can be seen from the image sequence with breath-holding.

Electric Impedance↗
PubMed1996

Zeneca ZD6169 activates ATP-sensitive K+ channels in the urinary bladder of the guinea pig.

The effects of Zeneca ZD6169, a tertiary carbinol, and levcromakalim were examined on the membrane potential of intact smooth muscle cells, and on ATP-sensitive K+ (KATP) channel currents in isolated smooth muscle cells from the guinea pig urinary bladder. ZD6169 and levcromakalim induced a glibenclamide-sensitive hyperpolarization of the membrane potential. The ZD6169- and levcromakalim-induced KATP currents were half-maximal at 1.02 and 2.63 mumol/l, respectively, with Hill coefficients of 1.46 and 1.62, respectively. The ZD6169-induced KATP currents were inhibited by internal ATP (3.0 mmol/l), reduced 34% by activators of protein kinase C, and decreased 35% when the external pH was lowered to 6.4. This study provides the first characterization of ZD6169 on KATP currents and indicates that ZD6169 is a potent opener of KATP channels in the smooth muscle from the urinary bladder.

Adenosine Triphosphate↗
PubMed1996

Factors affecting death at home in Japan.

Despite the wish of the Japanese people to spend their final moments at home, the percentage of deaths at home among elderly is decreasing. Moreover, large variations in this rate were observed over the country. The present ecological study analyzed the relationship between the percentage of deaths at home for decedents aged 70 and over, and demographic, medical and socioeconomic characteristics. The data published in 1990 by the Japanese National Government were analyzed by correlation, principal-component, and multiple linear regression analyses. The results showed that the percentage of deaths at home for decedents aged 70 and over was positively associated with the number of persons per household, and the area of floor space per house. The divorce rate, the national tax per capita, and the mean length of hospitalization for stroke showed a negative association with the percentage of deaths at home. In the prefectures where the crude death rates of stroke and senility were high, elderly were more likely to die at home. These results suggested the importance of the number of family caregivers, and the housing conditions for terminal care at home. This research may lead to improve home medical assistance which is still underdeveloped in Japan.

Aged↗
PubMed1996

Studies of the K(ATP) channel opening activity of the new dihydropyridine compound 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione in bladder detrusor in vitro.

The potassium (K+) channel opening activity of ZM244085 (9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione, CAS 149398-59-4), a novel dihydropyridine (DHP), was ascertained. In a set of functional assays, its mechanoinhibitory effect on myogenic activity of guinea pig bladder detrusor muscles, either mildly or highly depolarized with 15 or 80 mmol/l KCl, was measured. ZM244085 had negligible effect on the tone of the detrusor contracted with 80 mmol/l KCl but reduced the myogenic activity induced with 15 mmol/l KCl (IC50=4.2 +/- 0.4 mumol/l). Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, competitively antagonized this action of ZM244085 with a pA2 value of 7.6. This functional profile of ZM244085 is similar to that of the prototypic K+ channel opener cromakalim but stands in contrast to that of typical DHP Ca2+ channel blockers such as nifedipine and nimodipine. The membrane potential of the guinea pig detrusor, recorded with intracellular microelectrodes, was hyperpolarized 6.8 +/- 3.1 mV by ZM244085 (10 mumol/l). This hyperpolarization was completely blocked by glibenclamide but not affected by apamin (10 mumol/l), a toxin blocking specifically small conductance and Ca2+ dependent K+ (SKCa) channels. ZM244085 (10 mumol/l) increased the whole cell KATP current in isolated guinea pig detrusor cells by 8.8 +/- 2.5 pA, but failed to activate large conductance and Ca2+ dependent K+ (BKCa) channels in excised inside-out membrane patches from those cells. The results from these studies showed that ZM244085 is a K+ channel opener which activates predominantly KATP channels in vitro to relax bladder detrusors.

Acridines↗
PubMed1996

[A study on treatment of lung cancer by combined therapy of traditional Chinese medicine and chemotherapy].

From May 1992 to May 1995, 102 patients with lung cancer were divided randomly into two groups: group A, 48 patients, treated with combined therapy of TCM and chemotherapy, group B, 54 patients treated with chemotherapy alone. The protocol of chemotherapy used in the two groups was similar. The Chinese medicines were given according mainly to the Syndrome Differentiation. Four types were found in the group A: the Lung and Spleen Qi Deficiency type, the Lung Heat and Phlegm-Dampness type, the Lung-Yin and Stomach-Yin Deficiency type and the Qi stagnation and blood stasis type. The total effective rate according to the WHO standard was as follows: that of group A and group B was 52.1% and 35.1%; the 1 year survival rate of them was 69.4% and 66.7%, the 2 year survival rate was 56.2% and 15.8% and the median survival time were 13 months and 9 months, respectively. These results suggest that the elevation of median survival time and 2 year survival rate of group A might be closely related with the therapeutic effect of TCM, but the combined therapy of TCM and chemotherapy did not improve the therapeutic efficacy significantly.

Adult↗
PubMed1996

[Effect of bushen huayu recipe on DNA content of myeloid cells in aplastic anemia patients].

Quantification of myeloid cell-DNA in 30 cases with aplastic anemia (AA) was performed with computer image analysis techniquee pre- and post-treatmentally with Bushen Huayu recipe respectively, and compared with that of a control group of 30 healthy subjects. The results showed the average level of DNA in myeloid cells from AA patients was significantly lower than that of control (P < 0.01) prior to the treatment and it raised to the same level approximately as that of control after the treatment. This change of DNA quantity might result from the improvement of microcirculation or(and) stimulus to hematopoietical cells which accelerated the DNA anabolism in these cells.

Adolescent↗
PubMed1996

Cardiovascular effects of total soyasaponin in central nervous system and its relationship with monoamine transmitters.

AIM: To study the cardiovascular effect of total soyabeans saponins (TS) in brain and its relationship with monoamines. METHODS: After injection of TS (75 micrograms) into ventriculus lateralis cerebri (VLC) the changes of blood pressure (BP) and heart rate (HR) were observed and the contents of monoamines both in peripheral blood and brain (telencephalon, diencephalon, brainstem) were measured respectively by HPLC-ECD and fluorophotometry. RESULTS: After injection of TS into VLC, BP rise from 11.59 +/- 0.84 to 14.59 +/- 0.69 kPa; HR increased from 411 +/- 21 to 465 +/- 14 bpm; the contents of NE and E in peripheral blood increased from 6 +/- 3 to 64 +/- 44, from 6 +/- 2 to 38 +/- 34 nmol/L plasma, respectively, NE in brainstem increased from 14 +/- 0 to 18 +/- 3 nmol/g wet tissue respectively, but the contents of 5-HT in the 3 areas measured in the experiment decreased: in telecephalon from 9 +/- 1 to 5 +/- 1, in diencephalon from 14 +/- 2 to 7 +/- 2, in brainstem from 14 +/- 3 to 6 +/- 1 nmol/g wet tissue. CONCLUSIONS: The cardiovascular effects of TS in CNS were involved in the monoamine transmitters.

Animals↗
PubMed1995

Calcium dependent K-channels in guinea pig and human urinary bladder.

This study provides evidence for the presence of large conductance Ca(2+)-dependent K-channels in guinea pig and human urinary bladder smooth muscle. A23187, a Ca(2+)-ionophore, increased charybdotoxin and iberiatoxin sensitive 42K efflux in human urinary bladder smooth muscle cells, suggesting that large conductance Ca(2+)-dependent K-channels are present in these cells. NS004, a large conductance Ca(2+)-dependent K-channel opener, relaxed guinea pig bladder strips precontracted with 15 mM KCl which is inhibited by iberiatoxin. In addition, NS004 also evoked an iberiatoxin sensitive increase in 86Rb/42K efflux in guinea pig and human urinary bladder smooth muscle cells, demonstrating that NS004 activates large conductance Ca(2+)-dependent K-channels to achieve its relaxation effect in the bladder.

Animals↗
PubMed1995

Potent, orally active, competitive N-methyl-D-aspartate (NMDA) receptor antagonists are substrates for a neutral amino acid uptake system in Chinese hamster ovary cells.

A series of enantiomerically pure (phosphonomethyl)-substituted phenylalanine derivatives related to SDZ EAB 515 (1) were prepared as competitive N-methyl-D-aspartate (NMDA) receptor antagonists. Unlike most known competitive NMDA antagonists, analogs in this series with the S-configuration are potent NMDA antagonists whereas analogs with the unnatural R-configuration are weak NMDA antagonists, as determined by receptor binding experiments and their anticonvulsant action in mice. Examination in a previously reported competitive NMDA pharmacophore model revealed that receptor affinity can be explained partially by a cavity that accommodates the biphenyl ring of 1, while the biphenyl ring of the R-enantiomer 2 extends into a disallowed steric region. We proposed that analogs with the natural S-configuration and a large hydrophobic moiety would have an advantage in vivo over analogs with an R-configuration by being able to use a neutral amino acid uptake system to enhance both peripheral adsorption and transport into the brain. Examination in a system L neutral amino acid transport carrier assay shows that 1 competes with L-Phe for transport in an apparent competitive and stereospecific manner (estimated Ki = 50 microM). The 1- and 2-naphthyl derivatives 3a,3b were found to be among the most potent, competitive NMDA antagonists yet discovered, being ca. 15-fold more potent than 1 in vitro and in vivo, with a long duration of action. The title compound 3a had potent oral activity in MES (ED50 = 5.0 mg/kg). 3a also retains its ability to compete, albeit more weakly than 1 (estimated Ki = 200 microM), for L-Phe uptake to CHO cells. In this series, analogs with the R-configuration are not substrates for the system L neutral amino acid transport carrier. These results provide evidence that central nervous system active agents can be designed as substrates of a neutral amino acid transporter as a means to enhance penetration of the blood-brain barrier.

2-Amino-5-phosphonovalerate↗
PubMed1995

K-channel opening activity of ZD6169 and its analogs: effect on 86Rb efflux and 3H-P1075 binding in bladder smooth muscle.

Zeneca ZD6169, (S)-N-(4-benzoylphenyl)-3,3,3-trifluoro- 2-hydroxy-2-methylpropionamide, is a novel compound which relaxes urinary bladder smooth muscle in vitro. The effect of ZD6169 and two of its analogs on 86Rb efflux and 3H-P1075 binding in guinea pig bladder strips was investigated to characterize the K-channel opening properties of this compound. ZD6169 concentration dependently increased the rate of 86Rb efflux from guinea pig bladder strips. 86Rb efflux evoked by ZD6169 and its analogs was blocked by glibenclamide (30 muM) but not by charybdotoxin, apamin or alpha-dendrotoxin, suggesting that this compound activates KATP channels in guinea pig bladder. In addition, interaction of ZD6169 with KATP channels was also confirmed in human bladder smooth muscle cells. Specific binding of 3H-P1075, a potent opener of KATP channels, to guinea pig urinary bladder strips was observed. 3H-P1075 binding was inhibited by known KATP openers. ZD6169 inhibited binding of 3H-P1075 to urinary bladder strips like other structurally different KATP openers, e.g. cromakalim and pinacidil. Potencies for inhibition of 3H-P1075 binding by ZD6169 and other potassium channel openers correlate well with potencies for increase in 86Rb efflux and bladder muscle relaxation studies. It is concluded that Zeneca ZD6169 is a potassium channel opener which activates ATP-sensitive K-channels in guinea pig urinary bladder strips as well as in human bladder cells. Furthermore, binding studies suggest that the effects of ZD6169 and its analogs are mediated by binding to the site labeled by 3H-P1075 in guinea pig bladder strips.

Amides↗