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Biomedical subjects

Y P Sun

Publications and source records attributed to Y P Sun.

At least 19 recordsLinked to original sources

Structure determination and relative properties of novel noncentrosymmetric borates MM'4(BO3)3 (M = Na, M' = Ca and M = K, M' = Ca, Sr).

A series of novel noncentrosymmetric borates, MM'4(BO3)3 (M = Na, M' = Ca; M = K, M' = Ca, Sr), have been successfully synthesized via a standard solid-state reaction. The crystal structures have been determined by the SDPD (structure determination from powder diffraction) method. They crystallize in the noncentrosymmetric space group Ama2 with the following lattice parameters: a = 10.68004(11) A, b = 11.28574(11) A, c = 6.48521(6) A for NaCa4(BO3)3; a = 10.63455(10) A, b = 11.51705(11) A, c = 6.51942(6) A for KCa4(BO3)3; and a = 11.03843(8) A, b = 11.98974(9) A, c = 6.88446(5) A for KSr4(BO3)3. The fundamental building units are isolated BO3 anionic groups. Their second harmonic generation (SHG) coefficients were one-half (NaCa4(BO3)3), one-third (KCa4(BO3)3), and two-thirds (KSr4(BO3)3) as large as that of KH2PO4 (KDP). The infrared and UV-vis spectra of the three compounds are discussed. Moreover, a comparison of the structures of these novel compounds and three other novel cubic compounds with the same formula, MM'4(BO3)3 (M = Li, M' = Sr; M = Na, M' = Sr, Ba), is presented here.

Journal Article↗

Zona pellucida thickness and clinical pregnancy outcome following in vitro fertilization.

OBJECTIVE: To investigate possible correlations of ZPT or ZPTV with clinical outcome following in vitro fertilization. METHODS: Two hundred forty-six embryos were selected for transfer on day 3 with clear image record from 81 IVF-ET cycles. The laser system measurement software was used to measure the ZTP value of each embryo and the ZPTV was computed. Statistical analysis was done using the ANOVA or Chi-square test. RESULTS: Both ZPT and ZPTV declined with women's age. The mean ZPTV of embryos from patients between 30 and 34 years old was significantly higher than that from patients older than 35 (P<0.001). The ZPTV in pregnancy group was significantly higher than that in nonpregnancy group (P<0.005). The clinical pregnancy rate in the group with ZPTV more than 20% was significantly higher than that in the group with ZPTV less than 20% (P<0.05). The ZPTV of high grade embryos was significantly higher than that of low grade embryos (P<0.001). CONCLUSIONS: ZPTV rather than ZPT is an effective parameter to evaluate the embryo quality. Increasing the ZPTV may enhance embryo implantation potential.

Adult↗

Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains.

A metalloprotease and disintegrin (ADAM) is a family of membrane-anchored proteins and all family members have a multi-domain structure containing a zinc metalloprotease domain and a disintegrin domain that may serve as an integrin ligand. Here we reported two novel mammalian transcripts of Adam23, named Adam23 beta and Adam23 gamma, to be involved in the development and functional activities of mammalian brains. Adam23 gamma was isolated from a 22-week human fetal brain cDNA library, using an EST homologous to Adam as a probe, and is 100% homologous to human Adam23 (Adam23 alpha) except that it lacks a fragment of 91 bp near the C-terminal, thus it could not form obvious transmembrane domain. Adam23 beta was discovered while the diversity at the transmembrane domain (TM) was analyzed. Adam23 beta has a different sequence in the 91 nucleotides and thus encode different transmembrane domain. Adam23 beta and Adam23 gamma are mainly expressed in brain like Adam23 alpha. RT-PCR experiments in mouse brain also detected the two isoforms, consistent with observation of Northern analysis of human RNAs. Furthermore, results of RT-PCR amplification of Adam23 gamma in mouse brains of different developmental stages revealed a developmentally regulated expression pattern: Adam23 gamma is expressed in embryonic and infant brain, and disappeared after the 10th postnatal day. This temporally changing expression pattern of Adam23 gamma suggests that ADAM23 gamma likely plays an important role in brain development.

ADAM Proteins↗

Photoelectrocatalytic degradation of humic acid in aqueous solution using a Ti/TiO2 mesh photoelectrode.

Humic acid (HA) is one of natural organics existing in water supply as a precursor of trihalomethanes formation in chlorination. The photo-degradation of HA in aqueous solution by photoelectrocatalytic (PEC) oxidation using a Ti/TiO2 mesh electrode was investigated in terms of UV absorbance at 254 nm, colour and TOC concentration. The key factors affecting the PEC oxidation efficiency were studied, including the concentration of electrolyte, electrical bias applied. pH value of HA solution, the intensity of incident light and the area of Ti/TiO2 mesh photoelectrodes. The first-order kinetic model was applied to describe the PEC oxidation, in which the kinetic constant k was verified by the experimental data as a function of the concentration of electrolyte, light intensity, the area of Ti/TiO2 mesh electrode and the voltage of electrical bias applied. It was found that there was an optimal bias voltage of 1.63 V and low pH value was favourable for TOC removal in HA solution. Our investigation showed that PEC oxidation was a convenient way to mineralise the organic matters with high efficiency.

Coloring Agents↗

Enhancement of photocatalytic oxidation of humic acid in TiO2 suspensions by increasing cation strength.

This study aimed at improving the photocatalytic (PC) oxidation of humic acids (HA) in TiO2 suspensions by adding cationic ion such as calcium or magnesium. A set of tests was first conducted in the dark to study the adsorption of HA onto TiO2 in suspensions at different pH and calcium concentrations. The experiment demonstrated that the adsorption of HA onto the TiO2 particles was either pH-dependent or calcium strength-dependent due to electrostatic interaction and calcium ion bridging. The photodegradation of HA in the presence of UV irradiation was investigated as a function of pH and the concentration of calcium and magnesium ions. The results showed that the adsorption behavior between HA and TiO2 played a very important role during the PC oxidation process. The PC oxidation could be enhanced at neutral pH by increasing the cation strength. The kinetics of HA PC degradation in TiO2 suspensions with different initial concentrations was also studied using the Langmuir-Hinshelwood model.

Catalysis↗

Identification of dual cyclooxygenase-eicosanoid oxidoreductase inhibitors: NSAIDs that inhibit PG-LX reductase/LTB(4) dehydrogenase.

Eicosanoids play key roles in many physiologic and disease processes, and their regulation by nonsteroidal anti-inflammatory drugs (NSAIDs) is critical to many therapeutic approaches. These autacoids are rapidly inactivated by specific enzymes such as 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-reductase/leukotriene B(4) 12-hydroxydehydrogenase (PGR/LTB(4)DH) that act on main series of eicosanoids (i.e., leukotrienes, prostaglandins), and recently found to act in lipoxin inactivation. Here, a panel of NSAIDs was assessed to determine each compound's ability to inhibit eicosanoid-directed activities of either the recombinant 15-PGDH or the PG-LXR/LTB(4)DH. The recombinant 15-PGDH that acts on both prostaglandin E(2) (PGE(2)) and lipoxin A(4) (LXA(4)) was not significantly inhibited by the NSAIDs tested. In contrast, several of the widely used NSAIDs were potent inhibitors of the PG-LXR/LTB(4)DH that metabolizes 15-oxo-PGE(2), and LTB(4) as well as 15-oxo-LXA(4). Diclofenac and indomethacin each inhibited PG-LXR/LTB(4)DH-catalyzed conversion of 15-oxo-PGE(2) to 13,14-dihydro-15-oxo-PGE(2) by 70 and 95%, respectively. Also, a COX-2 inhibitor, niflumic acid, inhibited the PG-LXR/LTB(4)DH eicosanoid oxidoreductase (EOR) by 80% while other COX-2 inhibitors such as nimesulide and NS-398 did not inhibit this enzyme. These results indicate that certain clinically useful NSAIDs such as diclofenac and indomethacin, in addition to inhibiting cyclooxygenases (1 and 2), also interfere with eicosanoid degradation by blocking PG-LXR/LTB(4)DH (EOR) and are members of a new class of dual cyclooxygenase (COX)-EOR inhibitors. Moreover, they suggest that the impact of NSAIDs on PG-LXR/LTB(4)DH activities as targets in the local tissue regulation of eicosanoid-mediated processes should be taken into account.

15-Oxoprostaglandin 13-Reductase↗

Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Animals↗

An engineering assessment of the burning of the combustible fraction of construction and demolition wastes in a redundant brick kiln.

This paper confirms both technical feasibility and economic potential via the use of redundant brick kilns as an alternative option for disposal of the combustible fractions of construction and demolition wastes by a three-stage analysis. To assess such an idea, one brick kiln was selected for performing an engineering feasibility study. First of all, field sampling and lab-analyses were carried out to gain a deeper understanding of the physical, chemical, and thermodynamic properties of the combustible fractions of construction and demolition wastes. Kinetic parameters for the oxidation of the combustible fractions of construction and demolition wastes were therefore numerically calculated from the weight loss data obtained through a practice of thermogravimetric analyzer (TGA). Secondly, an engineering assessment for retrofitting the redundant brick kiln was performed based on integrating several new and existing unit operations, consisting of waste storage, shredding, feeding, combustion, flue gas cleaning, and ash removal. Such changes were subject to the operational condition in accordance with the estimated mass and energy balances. Finally, addressing the economic value of energy recovery motivated a renewed interest to convert the combustible fractions of construction and demolition wastes into useful hot water for secondary uses.

Construction Materials↗

Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function.

BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACE-I(s)) and angiotensin receptor blockers (ARB(s)) provide vascular protection. This study was designed to compare ACE-I(s) with widely differing tissue affinity (captopril and quinapril) and an ARB (losartan) on vascular protection against the adverse effects of high cholesterol. METHODS AND RESULTS: Forty-two New Zealand rabbits on a 0.5% cholesterol diet were randomized into control, captopril (10 mg/kg/d), quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril, quinapril, and losartan significantly attenuated aortic lipid lesions (P=0.001). Captopril and quinapril were more effective than losartan in preserving vascular relaxation. CONCLUSIONS: Captopril, quinapril, and losartan had similar protective effects against atherogenesis. Captopril and quinapril were more effective than losartan in preserving vascular function. Increased bradykinin by ACE inhibition may be responsible for this improved vascular endothelial function.

Angiotensin Receptor Antagonists↗

Secondhand tobacco smoke impairs rabbit pulmonary artery endothelium-dependent relaxation.

OBJECTIVES: To determine whether secondhand smoke (SHS) induces pulmonary artery endothelial dysfunction, and whether dietary L-arginine supplementation is preventive. BACKGROUND: SHS causes coronary and peripheral arterial endothelial dysfunction. METHODS: The effects of L-arginine supplementation (2.25% solution) and SHS (10 weeks) on pulmonary vascular reactivity were examined in 32 rabbits fed a normal diet. Endothelium-dependent relaxation of precontracted pulmonary artery segments was studied using acetylcholine and calcium ionophore. Endothelium-independent relaxation was studied using nitroglycerin. Endothelial and serum L-arginine levels were measured by chromatography. In eight SHS-exposed and in eight control rats, pulmonary artery nitric oxide synthase (NOS) activity and arginase activity were studied using the titrated arginine to citrulline conversion assay. RESULTS: SHS reduced maximal acetylcholine-induced (p = 0.04) and calcium ionophore-induced (p = 0.02) relaxation. L-Arginine increased maximal acetylcholine-induced (p = 0.047) vasodilation. SHS and L-arginine did not influence nitroglycerin-induced relaxation. SHS reduced endothelial L-arginine (p = 0.04) but not serum L-arginine. L-Arginine supplementation increased endothelial (p = 0.007) and serum L-arginine (p < 0.0005). Endothelium-dependent relaxation induced by acetylcholine and calcium ionophore varied directly with endothelial (r = 0.67, r = 0.67) and serum L-arginine (r = 0.43, r = 0.45), respectively. SHS reduced constitutive NOS activity (p = 0.03). CONCLUSIONS: SHS reduces pulmonary artery endothelium-dependent relaxation by decreasing NOS activity and possibly by decreasing endothelial arginine content. L-Arginine supplementation increases serum and endothelial L-arginine stores and prevents SHS-induced endothelial dysfunction. L-Arginine may offset the deleterious effect of SHS on pulmonary arteries by substrate loading of the nitric oxide pathway.

Animals↗

Calcitonin is expressed in gonadotropes of the anterior pituitary gland: its possible role in paracrine regulation of lactotrope function.

Previous studies from this laboratory have shown that salmon (S) calcitonin (CT)-like immunoreactive peptide (CTI) is synthesized and secreted by the anterior pituitary (AP) gland. These studies also co-localized CTI to gonadotropes, and demonstrated that SCT is a potent inhibitor of lactotrope function. However, the molecular structure of putative gonadotrope-derived CTI that inhibits lactotrope function has not been defined. The present studies cloned CT cDNA (pit-CT cDNA) from a mouse gonadotrope L beta T2 cell line using RT-PCR and rapid amplification of cDNA ends (RACE) techniques. Alignment of nucleotide sequences of pit-CT and mouse CT revealed greater than 99% homology between the sequences. The pit-CT cDNA was ligated into a mammalian expression vector, and the construct was transfected into L beta T2 cells. Two stable transfectant cell lines (CT.U6/A and B) were obtained by selection in G418. Subsequent S1-nuclease protection assay and immunocytochemistry results have shown that: (1) pit-CT peptide expressed by CT.U6 cell lines immunoreacted with GCT1-anti-SCT serum; (2) secretions of CT.U6 cells inhibited prolactin (PRL) release, PRL mRNA abundance and DNA synthesis of PRL-secreting GGH3 cells; and (3) CT.U6-induced inhibition was abolished by GCT1-anti-SCT serum. The studies also generated a riboprobe from the cloned pit-CT cDNA, and localized CT mRNA expression in gonadotropes of rat AP gland by in situ hybridization histochemistry. These results demonstrate that pit-CT mRNA is closely homologous to mouse CT mRNA; it is expressed by gonadotropes of the rat AP gland, and the peptide may significantly affect lactotrope function by inhibiting PRL release and cell proliferation.

Animals↗

[Roles of Galphaq/11 mediated- and platelet-derived growth factor mediated-signal transduction pathways in rat aorta restenosis].

To observe the roles of Galphaq/11 mediated- and platelet-derived growth factor (PDGF) mediated-signal transduction pathways in proliferation and migration of vascular smooth muscle cells (VSMC) after arterial injury, a vascular cell proliferation model was established by balloon injury in rat aorta and the morphologic changes in injured vascular walls after the injury were studied. Activities of angiotensin converting enzyme (ACE) and aorta phospholipase C (PLC) were tested, and levels of platelet-derived growth factor receptor-beta (PDGFR-beta) and Galphaq/11 protein were measured by Western blot analysis. At l day after operation, injured aortic segments showed denudation in endothelial cells. Medial VSMC proliferation and intimal hyperplasia were not observed. As compared with the sham group, ACE activities were increased by 382.7 percent; (P<0.0l), but the expression of PDGFR-beta and PLC activities did not show significant changes (P>0.05). In addition, the level of Galphaq/11 protein was decreased by 20.0 percent; (P<0. 05). At l4 days after operation, sections of injured aorta showed marked intimal thickening with large numbers of VMSCs proliferating throughout intima and media. In comparison with the sham group, ACE activity, PLC activity and the level of PDGFR-beta were increased by 420.2 percent; (P<0.01), 186.2 percent; (P<0.05) and 85.0 percent; (P<0.05), respectively. While the level of Galphaq/11 protein was decreased by 33.1 percent; (P<0.01). The above data suggest that the PDGF-mediated signal transduction pathway plays an important role in VSMC proliferation.

Angioplasty, Balloon↗

Mechanisms of vasorelaxation induced by eicosapentaenoic acid (20:5n-3) in WKY rat aorta.

The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 microM) in a concentration-dependent manner. Contractions induced by Bay K 8644 or increasing concentrations of calcium were unaffected by EPA. The relaxant effect of EPA (3 - 100 microM) was significantly inhibited by indomethacin (10 microM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 microM). Removal of the endothelium did not alter EPA-induced relaxations. In Ca(2+)-free, EGTA 2 mM solution, EPA (10 - 30 microM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 microM) diminished both NA-induced (1 microM) phasic and sustained contractions. The vasorelaxant effects of EPA (> or =30 microM) on NA-induced (1 microM) contractions were significantly inhibited by the K(+) channel blocker, glibenclamide (10 microM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1 - 100 microM) responses. These results indicate EPA exerts its endothelium-independent vasorelaxant effects in WKY rat aortae through production of prostanoids which activate K(+)(ATP) channels. Inhibition of Ca(2+) mobilization from intracellular pools and influx through the non-L-type, but not the L-type, Ca(2+) channel are also possible mechanisms action of EPA's.

Animals↗

Effects of cholesterol diets on vascular function and atherogenesis in rabbits.

Vascular endothelial dysfunction is an important early event in atherogenesis. To evaluate the effects of different levels of cholesterol-containing diets on vascular function and atherogenesis, 17 New Zealand White male rabbits were randomized into four groups: Control with noncholesterol, 10-week 0.5% (0.5C-10) or 1% cholesterol (1C-10), and 14-week 0.5% cholesterol (0.5C-14) feedings. After 10 or 14 weeks, the aortas were harvested for studies of vascular endothelial function and percentage surface lipid lesions. The 0.5% and 1% cholesterol feedings resulted in the same degree of hypercholesterolemia independent of the level and period of cholesterol feeding. There was a decreased trend in vascular endothelial-dependent relaxation to acetylcholine in cholesterol-fed rabbits. Fourteen-week cholesterol feeding induced the least vascular dilation at a concentration of 10-7 M acetylcholine (-38 +/- 3%, -23 +/- 4%, -23 +/- 2%, and -15 +/- 5% in control, 0.5C-10, 1C-10, and 0.5C-14 groups, respectively, P = 0.003). More cumulative exposure of arterial walls to cholesterol induced more surface lipid lesions in the aorta (r = 0.877, P < 0.001). There was a negative relationship between aortic lesions and vasodilation (r = -0.557, P = 0.020 for calcium ionophore; r = -0.463, P = 0.062 for acetylcholine). We conclude that the 0.5% and 1% cholesterol feedings induce similar degrees of hypercholesterolemia. However, aortic lipid lesions and vascular reactivity are dependent on cumulative exposure to cholesterol rather than serum cholesterol level only. Furthermore, decreased vascular endothelial relaxation in cholesterol-fed rabbits was related to lipid plaques in the aorta.

Analysis of Variance↗

[Alteration of the expression of rat cardiac Galphaq/11 and Gialpha2 proteins during endothelin-1 pre-treatment].

The present study was undertaken to explore the mechanism of G protein-mediated signal transduction pathway during endothelin-1 (ET-1) pre-treatment and ischemic preconditioning (IP). Rats were divided into four groups: ET-1, IP, ischaemia-reperfusion (IR) and control groups. ET-1 pre-treatment model was prepared by administrating 0.5 nmol/(L.kg) ET-1 into rat left ventricle, whereas IP model was prepared by ligating the left coronary artery for 5 min followed by 30 min reperfusion. All the animals were subjected to 60 min regional ischaemia and 30 min reperfusion alternately and then parameters of ventricular arrhythmia and expression of cardiac Galphaq/11 and Gialpha2 were measured. The results showed that the scores of ventricular arrhythmia decreased significantly in both ET-1 and IP treated groups as compared with IR group. In comparison with control group, Galphaq/11 increased by 77.8% (P<0.05) and 110.6% (P<0.01) in IP and ET-1 group respectively. Gialpha2 showed no significant difference in IP group, while it decreased by 31.0% (P<0.01) in ET-1 group. In conclusion, activation of G alphaq/11 may be related to the protecting mechanism of ET-1 pre-treatment and IP, whereas Gialpha2 may only play a role in ET-1 pre-treatment.

Animals↗

[Effects of acute hypobaric hypoxia on the distribution of somatostatin contents in lower gastrointestinal tract of rats].

OBJECTIVE: To examine the effects of acute hypobaric by hypoxia on the distribution of Somatostatin (SS) contains in lower gastrointestinal tract of rats. METHOD: 36 Wistar [correction of Wister] male rats were divided into 6 groups. Three were control groups, three were ulcerous groups. Each group contains ground, 5000 m above sea level and 10000 m above sea level. SS contents were determined with radioimmunoassay [correction of radioimmunoassy] methods. RESULT: Statistically significant difference was exhibited among each group. There was no significant difference of SS contents in each altitude between model and control. SS contents were significantly increased in intestine of control in 5000 m groups, in caecum in 5000 m groups, compared with that in ground (P<0.05). It was also significantly increased in intestine of model in 5000 m groups, in caecum in 5000 m groups, compared with that in ground (P<0.01). SS contents was significantly increased in caecum of model in 10000 m groups compared with that in ground (P<0.05). Except this, There was no significant difference of ss contents in lower gastrointestinal tract among each group. CONCLUSION: SS contents in lower gastrointestinal tract were significantly increased in acute hypobaric hypoxia rats. This result suggested that ss contents in lower gastrointestinal tract may play an important protective role in acute hypobaric hypoxia rats.

Altitude↗

Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations.

BACKGROUND: Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death (apoptosis). We investigated the effects of As2O3 on a panel of malignant lymphocytes to determine whether growth-inhibitory and apoptotic effects of As2O3 can be observed in these cells at clinically achievable concentrations. METHODS: Eight malignant lymphocytic cell lines and primary cultures of lymphocytic leukemia and lymphoma cells were treated with As2O3, with or without dithiothreitol (DTT) or buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis). Apoptosis was assessed by cell morphology, flow cytometry, annexin V protein level, and terminal deoxynucleotidyl transferase labeling of DNA fragments. Cellular proliferation was determined by 5-bromo-2'-deoxyuridine incorporation into DNA and flow cytometry and by use of a mitotic arrest assay. Mitochondrial transmembrane potential (delta psi(m)) was measured by means of rhodamine 123 staining and flow cytometry. Protein expression was assessed by western blot analysis or immunofluorescence. RESULTS: Therapeutic concentrations of As2O3 (1-2 microM) had dual effects on malignant lymphocytes: 1) inhibition of growth through adenosine triphosphate (ATP) depletion and prolongation of cell cycle time and 2) induction of apoptosis. As2O3-induced apoptosis was preceded by delta psi(m) collapse. DTT antagonized and BSO enhanced As2O3-induced ATP depletion, delta psi(m) collapse, and apoptosis. Caspase-3 activation, usually resulting from delta psi(m) collapse, was not always associated with As2O3-induced apoptosis. As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens. CONCLUSIONS: Substantial growth inhibition and apoptosis without evidence of differentiation were induced in most malignant lymphocytic cells treated with 1-2 microM As2O3. As2O3 may prove useful in the treatment of malignant lymphoproliferative disorders.

Adenosine Triphosphate↗

Present status of the total artificial heart at the University of Tokyo.

At the University of Tokyo, various types of total artificial heart (TAH) systems have been studied since 1959. At the present time, 2 types of implantable TAH have been developed. One is an undulation pump TAH (UPTAH) and the other is a flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of implantation were performed in goats and 10 days' survival obtained. The new type of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane membrane valve, a jellyfish valve, has been developed. The longest in vivo experiences with this valve in the TAH blood pump have been 312 days in the left side blood pump and 414 days in the right side blood pump. Conductance and arterial pressure based control (1/R control) can realize the physiological control of the TAH. Using 1/R control, 532 days of survival could be obtained in a goat with a paracorporeal TAH. The technique required to apply this control method to a implantable TAH is under development. We have proposed a new 5 year research project of the implantable TAH entitled "Comprehensive Basic Research on the Development of a Japanese Original Implantable Total Artificial Heart" to The Ministry of Welfare.

Animals↗