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Biomedical subjects

L J Chen

Publications and source records attributed to L J Chen.

At least 91 records · Page 5Linked to original sources
PubMed1990

Selective cytotoxicity against human tumor cells by an anti-gastric cancer monoclonal antibody-mitomycin C conjugate.

An anti-gastric cancer monoclonal antibody, MGb2, was chosen to prepare MGb2-mitomycin C (MMC) conjugate. Four to five molecules of MMC were introduced into each molecule of antibody with the antibody activity well retained. The conjugate showed a highly selective cytotoxicity upon human gastric cancer cells KATO-III. In the 48-h exposure test, the cytotoxic effect of MGb2-MMC upon target cells was similar to that of free MMC, but much greater than that of normal mouse immunoglobulin-MMC conjugate. Instead, the MGb2-MMC showed a statistically less cytotoxic effect upon non-target cells. Imaging and biodistribution studies indicated that the MGb2 was still well localized in tumor tissue after its conjugation with MMC.

Animals↗
PubMed1990

[Effects of immuno-drug conjugates on growth of human gastric cancer xenograft in subrenal capsule of nude mice].

A conjugate of an anti-gastric cancer monoclonal antibody and mitomycin C linked by polyaldehyde dextran T-40 (MGb2-PAD-MMC) was prepared. Nude mice inoculated with human gastric cancer (SGC-7901) xenograft in bilateral subrenal capsule were treated ip with the conjugate at a daily dose containing MGb2 22.4 mg/kg and MMC 1 mg/kg for 6 d since 4 h after inoculation. The efficacy of the conjugate was estimated by the reduction of tumor size which calculated by T/C (%) was 32.2%. If MGb2 in the conjugate was replaced by a normal nude mice IgG (NIgG-PAD-MMC) or the nude mice were treated ip with the dose of MMC alone, the tumor T/C (%) were 58 and 87%, respectively. It was statistically significant between MGb2-PAD-MMC and NIgG-PAD-MMC or MMC treatment. When the above mentioned nude mice with SGC-7901 were treated ip with thrice dose of the conjugate (MGb2 67.2 mg/kg and MMC 3 mg/kg) for 6 d, the tumor growth was inhibited completely. Nevertheless, the same dose of MMC was given to the nude mice resulted in toxic appearance included anorexia, weight loss or even death. Furthermore, when the nude mice were treated ip with MGb2-PAD-MMC 24 h after inoculation, no apparent therapeutic effect was seen. In some experiments, nude mice inoculated with another human transplanted gastric tumor (GA II) xenograft treated ip with a conjugate of MGb2 and MMC or daunorubcin (Dau) 1 day after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1989

Rat liver ATP-sulfurylase: purification, kinetic characterization, and interaction with arsenate, selenate, phosphate, and other inorganic oxyanions.

ATP-sulfurylase (ATP:sulfate adenylyltransferase; EC 2.7.7.4), the first enzyme of the two-step sulfate activation sequence, was purified extensively from rat liver cytosol. The enzyme has a native molecular mass of 122 +/- 12 kDa and appears to be composed of identical 62 +/- 6-kDa subunits. At 30 degrees C and pH 8.0 (50 mM Tris-Cl buffer containing 5 mM excess Mg2+), the best preparations have "forward reaction" specific activities of about 20 and 2 units X mg protein-1 with MoO4(2-) and SO4(2-), respectively. The reverse (ATP synthesis) specific activity is about the same as the forward molybdolysis activity. The kinetic constants under the above conditions are as follows: KmA = 0.21 mM, Kia = 0.87 mM, KmB = 0.18 mM, KmQ = 0.65 microM, Kiq = 0.11 microM, and KmP = 5.0 microM where A = MgATP, B = SO4(2-), Q = APS, and P = total PPi at 5 mM Mg2+. PPi is a mixed-type inhibitor with respect to MgATP and SO4(2-). SeO4(2-) is an alternative inorganic substrate with a Vmax about 20% that of SO4(2-). The product, APSe, is unstable. But in the presence of a sufficient excess of APS kinase, APSe is completely converted to PAPSe. The rate constant for nonenzymatic PAPSe hydrolysis was determined from measurements of the final steady-state reaction rate in the presence of limiting initial SeO4(2-) and a large excess of MgATP, ATP sulfurylase, APS kinase, and the other coupling enzymes and their cosubstrates. The results yielded a k of 2.4 +/- 0.5 X 10(-3) sec-1 (t1/2 ca. 5 min). Phosphate is an effective buffer for enzyme purification and storage but inhibits catalytic activity, particularly at low substrate concentrations. In the presence of buffer levels of Pi, the MgATP reciprocal plot of the SO4(2-)-dependent reaction is concave-up. Inorganic monovalent oxyanions are dead end inhibitors competitive with SO4(2-) and apparently uncompetitive with respect to MgATP. The relative potencies are in the order ClO3- greater than ClO4- greater than FSO3- greater than NO3-. Thiosulfate is also competitive with SO4(2-) but noncompetitive with respect to MgATP. Several divalent oxyanions (MoO4(2-), WO4(2-), CrO4(2-), and HAsO4(2-] promote the enzyme-catalyzed cleavage of MgATP to AMP and MgPPi. The ratio Vmaxf/KmA ranged from 0.7 to 200 for various reactive inorganic substrates. The cumulative results suggest the random binding of MgATP and the inorganic substrate but the ordered release of MgPPi before APS.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Phosphosulfate↗
PubMed1989

[A clinical analysis of 18 cases with adult respiratory distress syndrome].

18 cases with adult respiratory distress syndrome (ARDS) admitted to our hospital since 1985 were reported. Among them, 2 cases were mild, 10 moderate and 6 severe. All of them received a combination of treatment, including correction of primary disease, O2 therapy, medications such as corticosteroid diuretics and anti-inflammatory agents, restriction of water intake and keep of negative fluid balance. Mechanical ventilation, especially early application of PEEP, was applied in 12 cases. In general, the level of pressure was kept between 0.08-0.1 KPa. End inspiration pause (EIP) was also routinely taken. Usually, the pausing period accounted for 10% of the respiratory cycle. 2 died among the 12 cases with mechanical ventilation, whereas all of the 6 cases receiving simple artificial ventilation died. The mortality rate was 44%.

Adult↗
PubMed1989

[Reproductive toxicity of bimolane in mice and rabbits].

Bimolane (AT-1727), 1,2-bis (4-morpholinomethyl-3,5-dioxopiperazinyl)-ethane, is a new antitumor drug, synthesized first in our institute. When the mice were injected ip bimolane 3.7 or 37.2 mg/kg on d 6-15 after mated, 23 or 100% of the embryos were resorbed, while the surviving fetuses remained normal. After ip bimolane 7.4 or 14.9 mg/kg, the weights of living fetuses were all less than that of the control group (P less than 0.01). After ig bimolane 140 mg/kg to the mice on d 6-15 after mated, 43% of the fetuses developed subcutaneous edema, but no other abnormalities were seen. When the rabbits were given ip bimolane 30 mg/kg on d 7-18 after mated, all the embryos were resorbed. On d 10 after mated ip a single dose of bimolane 74.4 mg/kg to the mice caused nanomelia (34%) and subcutaneous hematoma (55%). Therefore, teratogenicity of bimolane was observed in mice.

Animals↗
PubMed1988

Recognition of prokaryotic transcription terminators by spinach chloroplast RNA polymerase.

To determine whether chloroplast RNA polymerase will accurately terminate transcription in vitro, we have fused the spinach chloroplast rbcL promoter to the 3' end of the rbcL gene as well as to various factor independent transcription terminators from E. coli. Transcription of the rbcL minigene did not result in production of the expected 265 nucleotide RNA. However, the spinach chloroplast RNA polymerase did terminate transcription with varying efficiency at the thra, rrnB, rrnC and gene 32 terminators. The most efficient transcription termination was observed for the threonine attenuator. For each of the prokaryotic terminators, the chloroplast enzyme ceased transcription at essentially the same position as the E. coli RNA polymerase. These data indicate that the transcription termination process in chloroplasts has some features in common with the mechanism used in prokaryotes.

Base Sequence↗
PubMed1988

Sexual differentiation of rat hepatic bile salt sulfotransferase isoenzymes.

The mature female rat has three times the hepatic bile salt sulfotransferase (BSS) activity compared with male rats. This study examined the changes in two hepatic BSS isoenzyme activities during sexual maturation, and the role of estrogen in development of sex differences in BSS activities in mature rats. DEAE-Sephadex A-50 chromatography of hepatic cytosol from prepubescent pups revealed that more than 90% of total BSS activity was due to BSS I activity relative to BSS II, similar to postpubertal females. Sex differences in total BSS activities and the isoenzyme patterns developed after the onset of puberty at 30-35 days of age. BSS I was still the predominant isoenzyme in the adolescent female, similar to the prepubescent pup and mature female. In contrast, BSS I activity declined in adolescent males, which appeared to explain the fall in total BSS activity to only one-third of that of the female by maturity. BSS II activity was similar in both sexes at any age. Estrogen treatment of postpubertal male rats rapidly increased hepatic BSS capacity by enhancing BSS I activity producing an isoenzyme pattern similar to the mature female. This rapid enhancement of BSS I by estrogen was blocked by actinomycin D and puromycin. We concluded that 1) sex differences in BSS activities that develop during adolescence were in part due estrogen-maintaining BSS I activity in females and 2) estrogen regulates the synthesis of BSS I at a translational (or pretranslational) level.

Animals↗
PubMed1985

Purification and characterization of bile salt sulfotransferase from human liver.

Bile salt sulfotransferase, the enzyme responsible for the formation of bile salt sulfate esters, was purified extensively from normal human liver. The purification procedure included DEAE-Sephadex chromatography, taurocholate-agarose affinity chromatography, and preparative isoelectrofocusing. The final preparation had a specific activity of 18 nmol min-1 mg protein-1, representing a 760-fold purification from the cytosol fraction with a overall yield of 15%. The human enzyme has a Mr of 67,000 and a pI of 5.2. DEAE-Sephadex chromatography of the cytosol fraction revealed only a single species of activity. The limiting Km for the sulfuryl donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), is 0.7 microM. The limiting Km for the sulfuryl acceptor, glycolithocholate (GLC), is 2 microM. Reciprocal plots were intersecting. Product inhibition studies established that adenosine 3',5'-diphosphate (PAP) was competitive with PAPS (Ki = 0.2 microM) and noncompetitive with respect to GLC. GLC sulfate was competitive with GLC (Ki = 2.2 microM) and noncompetitive with respect to PAPS. Also, 3-ketolithocholate, a dead-end inhibitor, was competitive with GLC (Ki = 0.6 microM) and noncompetitive with respect to PAPS. Iso-PAP (the 2' isomer of PAP) was competitive with PAPS (Ki = 0.3 microM) and noncompetitive with GLC. The cumulative results of the steady-state kinetics experiments point to a random mechanism for the binding of substrates and release of products. The purified enzyme displays no activity toward estrone, testosterone, or phenol. Among the reactive substrates tested, the Vmax/Km values are in the order GLC greater than 3-beta OH-5-cholenic acid greater than glycochenodeoxycholate greater than glycocholate. p-Chloromercuribenzoate inactivated the enzyme. Either PAPS or GLC protected against inactivation, suggesting the presence of a sulfhydryl group at the active site.

Adenosine Diphosphate↗
PubMed1982

Development and regulation of bile salt sulfotransferase in rat liver.

Hepatic bile salt sulfotransferase activity was extremely limited in fetus, gradually increasing after birth. At puberty, enzyme activity declined in males but not in females, suggesting the influence of gonadal hormones associated with sexual maturation. Extremely high enzyme activity was found in pregnant rats at term. The neonatal bile salt sulfotransferase activity could be stimulated by bile acid feeding during pregnancy or maternal bile duct ligation. In contrast, a decrease in enzyme activity was detected in the treated pregnant females. Phenobarbital treatment during pregnancy also produced a 5-fold increase in neonatal enzyme activity. These results suggested that bile salt sulfation was regulated by chemical factors before maturity, and by gonadal hormones thereafter. Two fractions with bile salt sulfotransferase activity were separated from female liver by zone electrophoresis and DEAE-Sephadex A-50 chromatography, while a single active fraction was detected in male liver which corresponded to one of the active female fractions. The two active fractions in the female exhibited the same molecular weight (130 000), and different isoelectric points (6.8 and 5.3). The male fraction had a molecular weight of 130 000 and a pI of 5.3.

Aging↗
PubMed1982

Bile salt sulfotransferase in guinea pig liver.

Bile salt sulfotransferase from guinea pig liver is purified by the procedures of ammonium sulfate fractionation, Sephadex G-100 column chromatography, agarose-hexane-adenosine 3',5'-diphosphate affinity chromatography and polyacrylamide gel electrophoresis. The purified enzyme exhibits a pH optimum of 6.8, an isoelectric point of 5.6 and a molecular weight of 76 000 estimated by gel filtration technique. The apparent Km values of the enzyme are 7.7.10(-5) M for taurolithocholate and 1.4.10(-6) M for 3'-phoshoadenosine 5'-phosphosulfate. It requires Mg2+ and free sulfohydryl group(s) for activity. The enzyme reacts with hydroxy groups of bile salts at both 3 alpha and 3 beta positions. No activity is found in the kidney of guinea pig. The purified enzyme does not react with estrone, estradiol, testosterone, dehydroepiandrosterone, cholesterol, phenol, tryamine, and serotonin. The results indicate that bile salt sulfotransferase is distinct from other hepatic sulfotransferases.

Animals↗
PubMed1979

On the pathogenicity of Entamoeba histolytica. Part I: The role of bacterial associate on the modification of virulence of E. histolytica.

Of the 3 strains of Escherichia coli used, only Milner A strain was found capable of modifying the virulence of Entamoeba histolytica. None out of twenty-four hamsters inoculated with either 5 X 10(5) of axenically-cultured E. histolytica of NIH: 200 strain, or 1 X 10(7) of Esch. coli (A, B or C strains), was found to have amebic liver abscess. Whereas one out of six hamsters inoculated with the same number of amebae preincubated for 12 hrs with Esch. coli of Milner A strain was found to have abscess. The role of bacterial associate seems to be nothing but provides a more suitable environment for amebae, thus enable them to survive longer and endow them more time to adapt themselves to the given new environment. From liver abscess E. histolytica was recovered and successfully reaxenized. These amebae were capable of producing liver abscess, therefore the virulence seemed to be inheritable.

Animals↗