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Biomedical subjects

D Li

Publications and source records attributed to D Li.

At least 901 records · Page 50Linked to original sources
PubMed1989

Induction of cytochromes P450IIE1 and P450IIB1 by secondary ketones and the role of P450IIE1 in chloroform metabolism.

It has been shown previously that the potentiation of chloroform-induced hepatotoxicity by linear secondary ketones increases with the carbon-chain length. The present work examines the possibility that this potentiation is due to the induction of P450IIE1. The metabolism of chloroform, as measured using headspace gas chromatography, in the presence of microsomes from acetone-treated rats was elevated threefold compared to controls. Inclusion of monoclonal antibody against P450IIE1 inhibited the metabolism by 81%. Alternate substrates of P450IIE1 were also inhibitory. Chloroform metabolism was observed using purified, reconstituted P450IIE1 plus cytochrome b5, but was not detected using P450IIB1. The inductive effect of 18-hr oral pretreatment (15 mmol/kg body wt) with each of three secondary ketones on two isozymes of rat liver microsomal cytochrome P450, P450IIE1, and P450IIB1 was studied. The content of total microsomal P450 and NADPH-dependent cytochrome c reductase, the rates of oxidation of N-nitrosodimethylamine, benzphetamine, and pentoxyresorufin, as well as levels of immunoreactive protein for both of the isozymes were elevated by the pretreatments in the rank order of acetone less than or equal to 2-butanone less than 2-hexanone, in agreement with other trends noted by previous investigators. The results provide further evidence for the role of P450IIE1 induction in the potentiation phenomenon.

Animals↗
PubMed1989

Selective chromosomal damage and cytotoxicity of 125I-labeled monoclonal antibody 17-1a in human cancer cells.

A monoclonal antibody, 17-1a, which reacts with antigen expressed in human colon cancers was radiolabeled in high specific activity with 125I. The combination of the antibody and this radionuclide was observed to elicit specific cellular damage after being internalized into cells of the SW1116 human colon cancer cell line. The degree of internalization was quantitatively measured and found to increase over time to 49% after a 48-h incubation period. During this period, significant chromosome aberrations were observed in the SW1116 cell line due to the Auger electrons of 125I. This damage was not observed using Na125I, a nonimmunoreactive radiolabeled antibody, or cells which did not contain the requisite antigen. The number of chromosomal aberrations increased with increasing radioactive concentration of 125I-17-1a. The nuclear damage resulted in specific cellular cytotoxicity and decreased cell survival of SW1116 cells exposed to various concentrations of 125I-17-1a.

Antibodies, Monoclonal↗
PubMed1989

Positron emission tomography in manganese intoxication.

We employed 6-fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6-fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed.

Adult↗
PubMed1989

Effect of 1,3-butanediol on rat liver microsomal NDMA demethylation and other monooxygenase activities.

The administration of 1,3-butanediol (BD) previously has been shown to elevate blood concentrations of ketone bodies, to potentiate carbon tetrachloride hepatotoxicity, and to increase the hepatic microsomal content of cytochrome P450 and the activity of aniline hydroxylase. In the present study, oral treatment (10 g/kg) with racemic BD and each of its enantiomers (R-BD and S-BD) induced NDMA demethylase activity by approx. 1.5-fold in rat hepatic microsomes obtained 12 h later, suggesting an induction of P450IIE1, the acetone/ethanol-inducible form of P450. The results agreed with an immunochemically determined increase in the levels of this isozyme. No change in P450 content, NADPH-cytochrome-c reductase, or in pentoxyresorufin dealkylase activity were detected. Blood levels of acetone were determined during a 10-h period after BD administration and showed a higher initial rate of increase by R-BD, possibly due to steroselective metabolic oxidative metabolism. However, no difference in the induction of NDMA demethylase activity by the enantiomers could be detected. Induction of P450IIE1 probably contributes to the previously described potentiation of haloalkane-induced hepatotoxicity by BD administration.

Acetone↗
PubMed1989

Reduced accumulation of I-compounds in liver DNA of rats fed a choline-devoid diet.

Groups of rats were fed for 1, 4 or 7 months choline-devoid or choline-supplemented diets, that provided approximately 50% of the methionine, and 0.15% or 150% of the choline requirements of young, growing rats. Liver DNA was isolated and analyzed by the nuclease P1-enhanced version of the 32P-postlabeling assay, which detects aromatic/hydrophobic DNA adducts and I-compounds (adduct-like DNA modifications shown to accumulate in tissue of aging rats). DNA adducts and qualitative differences in the patterns of I-compounds were not observed in rats fed the two diets. However, in rats fed the choline-devoid diet there was a drastic reduction in the accumulation of I-compounds, compared with that in rats fed the control diet. These results extend previous evidence of a lack of relevant DNA adducts in the liver of rats fed the choline-devoid diet, and suggest the possibility of a role of I-compounds in the carcinogenicity of this diet.

Animals↗
PubMed1989

Regional cerebral glucose metabolism in three sets of identical twins with psychotic symptoms.

Three sets of young identical twins where at least one had a psychotic episode were assessed in terms of psychiatric and psychological status and integrity of cerebral structure and metabolism. The psychiatric diagnoses for each set were normal/schizophrenia, prodromal/schizophrenia and schizoaffective/schizoaffective. The latter two sets were re-examined two years after the initial assessment. The data are considered from a case study perspective. Reduced cerebral metabolism was found for at least one region on eight of nine scans of patients with a psychotic history. On seven of the nine scans, glucose metabolism in the orbital frontal cortex was reduced. These findings are discussed with respect to previous studies of glucose metabolism in patients with schizophrenia, metabolic similarities found in normal identical twins and the known functional specialization of the orbital frontal cortex.

Bipolar Disorder↗
PubMed1989

Correlates of arterial oxygenation during exercise in severe chronic obstructive pulmonary disease.

In the present study, we have undertaken a detailed analysis of the respiratory physiologic correlates of SaO2 during mild constant-load exercise in 38 patients with severe but stable COPD. Several respiratory physiologic variables that would be expected to influence exercise SaO2 were entered into a stepwise multiple linear regression analysis with mean exercise SaO2 as the dependent variable. Two variables (Dco and resting SaO2) were found to correlate strongly with mean exercise SaO2 (multiple r = 0.80; p less than 0.00001) and accounted for 65 percent of the variability among patients. The PaCO2 influenced resting SaO2 but had no independent influence on exercise SaO2. Subsequently, the model of mean exercise SaO2 derived in the present analysis was found to accurately predict mean exercise SaO2 in a group of 19 similar patients (r = 0.85; p less than 0.0001). While these findings do not establish a cause-and-effect relationship, they may provide clinicians with further insight as to which patients are likely to desaturate during exercise.

Aged↗
PubMed1989

MR imaging of periventricular leukomalacia in childhood.

Eight children with clinical and radiologic abnormalities consistent with periventricular leukomalacia were investigated with MR imaging of the brain that employed both inversion-recovery and T2-weighted spin-echo imaging sequences. The more precise delineation of white and gray matter on inversion-recovery images as compared with CT allows a detailed demonstration of the anatomic features of periventricular leukomalacia; specifically, a reduced quantity of white matter in the periventricular region and centrum semiovale and, in more severe cases, cavitated infarcts that replace the immediate periventricular white matter. The T2-weighted spin-echo and short inversion time inversion-recovery images demonstrated abnormally increased signal in white matter that appeared normal on CT scans and only minimally abnormal on conventional inversion-recovery images. These abnormalities most probably represent white matter gliosis that extends beyond the immediate periventricular regions. MR recognition of cerebral white matter abnormalities associated with periventricular leukomalacia may confirm the clinical suspicion of this diagnosis in children with spastic diplegia or quadriplegia.

Adolescent↗
PubMed1989

Subtle huge intervertebral disc herniation.

The accuracy of computerized tomography (CT) in diagnosing herniated discs has been well established. Huge herniated discs, which paradoxically may be very subtle, have been mentioned but not stressed as potential causes of false-negative diagnosis. Five cases during a 5-year period encompassing approximately 2500 examinations have been encountered by the authors. In this experience, the most consistent finding is the subtle increased density of the disc compared with the dural sac. The diagnosis is aided by awareness that huge discs severely compressing the dural sac may be very subtle; the use of narrower windows for CT scanning, sagittal re-formation, and occasionally the use of myelography with or without repeat CT scanning may also assist.

Adult↗
PubMed1989

Human breast carcinoma cell levels of MDR-1 (P-glycoprotein) transcripts correlate in vivo inversely and reciprocally with tumor progesterone receptor content.

Sixteen human breast carcinomas were subjected to molecular biological and biochemical analyses to determine tumor cell MDR-1 (P-glycoprotein) levels and progesterone receptor content. The results of these analyses disclosed a strong reciprocal and inverse correlation between levels of tumor cell-specific MDR-1 complementary hybrids and progesterone receptor content. These results suggest that the mechanisms which control expression of the P-glycoprotein gene and the progesterone receptor are interrelated and antagonistic, a result with obvious molecular biological, physiological, and clinical implications.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

[Quantitative determination of 5 alkaloids in plants of Coptis from China].

Quantitative determination of berberine, coptisine, palmatine, jatrorrhizine and epiberberine in Coptis chinensis, C. deltoidea, C. teetoides, C. omeiensis, C. chinensis var. brevisepala, C. linearisepala, C. gulinensis, C. chinensis var. unguiculata, C. teeta and 5 different samples of C. chinensis was made by thin layer chromatography-densitometry.

Alkaloids↗
PubMed1989

Study on some biologically active coordination compounds of metal ions (I)--Synthesis, characterization, structure and antitumor activity of complex of 3,6-di-(dimethylamino)-dibenzopyriodonium lanthanum EDTA.

The title coordination compound has been synthesized by the reaction of HLaEDTA.7H2O with (formula; see text) in ethanol aqueous solution. The single crystal has grown from aqueous solution and has been characterized by IR, TG-DTA, X-ray powder diffraction, molar conductance, UV and 1H-NMR. The determination of its crystal and molecular structure shows that it crystallizes in space group P21/n with lattice parameters: a = 14.735A, b = 29.335A, c = 16.409A, beta = 99.24 degrees, v = 7009.30A3, z = 4, F(000) = 3488, molecular weight M = 1756.90, Dc = 1.665g/cm3. It has been refined by the full matrix least squares method to final discrepancy factor R = 0.096. The anion [La2(EDTA)2(H2O)4]2- turns out to be a dimer, in which each of the two EDTA4- ions is coordinated to a La3+ ion with five of its six coordinating sites and the remaining sixth one--the oxygen atom of carboxylis bridged to two La3+ ions, thus forming a parallelogrammic four-membered ring La2O2. The nine coordinations about each metal are completed by two water molecules. The average bond length is 2.560 A for La-O and 2.833A for La-N. Approximately, the dimer belongs to point group Ci with the centre of inversion at the centre of La2O2 parallelogram. The antitumor activity of the coordination compound was studied by observing its effect on the incorporation of 3H-TdR into DNA of leukemia (L7712) cells in vitro. The degree of inhibition reached 83.9% after exposing 2 X 10(5) cells per millilitre to 4 X 10(-5) mol/L of the compound for 24 h, being higher than those of its precursors.

Antineoplastic Agents↗
PubMed1988

The corpus callosum is larger with right-hemisphere cerebral speech dominance.

Variations in the size of the human corpus callosum were examined as a possible morphological substrate of functional asymmetries of the cerebral hemispheres, such as cerebral speech dominance. The midsagittal surface area of the corpus callosum, obtained by magnetic resonance imaging, was measured in 50 patients with epilepsy and 50 neurologically normal control subjects. The mean callosal area did not differ significantly between patients and control subjects, between left-handed and right-handed subjects, or between men and women. When measurements were compared among 44 patients, whose cerebral speech dominance had been determined by the intracarotid injection of sodium amytal, the area of the corpus callosum was significantly greater in patients with right-hemisphere cerebral speech dominance. The mean callosal area was greater by 109 to 159 square millimeters (18-28%) when compared to that of patients with either left-hemisphere speech dominance or bilateral speech representation. This difference in midsagittal surface area could represent as many as 37 to 54 million additional callosal axons in subjects with right-hemisphere cerebral speech dominance.

Adolescent↗
PubMed1988

Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix.

Freshly isolated adult rat hepatocytes, when cultured on type I collagen (commercially available as Vitrogen), assume a polygonal shape, form a stable monolayer within 24 hours, but lose the capacity to express some liver-specific functions over time in culture. We incubated hepatocytes in a serum-free medium on a reconstituted basement membrane gel, "matrigel" (prepared from an extract of extracellular matrix of the murine Engelbreth-Holm-Swarm sarcoma), and observed that the cells adhered firmly, remained rounded as single cells or clusters, and maintained liver-specific gene expression for more than 1 week in vitro. Hepatocytes on matrigel secreted substantially higher amounts of albumin, transferrin, haptoglobin, and hemopexin, Northern blot analyses of extracted cellular RNA, expressed increased amounts of mRNA for the liver-specific protein albumin (as compared with cells on vitrogen). In cultures treated with phenobarbital, cytochrome P-450b, and cytochrome P-450e, mRNAs and proteins were barely detectable in cells on Vitrogen but were induced to levels similar to those in the liver in vivo in matrigel cultures. Likewise, the use of matrigel greatly enhanced the induction of mRNA and protein for P-450c by 3-methylcholanthrene and for P-450p by steroidal and nonsteroidal inducers. However, neither substratum permitted induction of P-450d by 3-methylcholanthrene, suggesting that the effects of matrigel are selective even for expression in liver of members of the superfamily of cytochrome P-450 genes. Within 5 days in cultures on Vitrogen, hepatocytes expressed detectable amounts of fetal liver aldolase activity and also mRNA for vimentin and type I collagen, each considered a phenotypic change reflecting hepatocyte "dedifferentiation." None of these was present in cells on matrigel. Responsiveness to mitogenic stimuli, as judged by incorporation of 3H-thymidine into DNA, was also decreased in hepatocytes cultured on matrigel. Finally, there was a remarkable increase in the levels of both matrices during the first 2 days in culture. However, the continuously cytoskeleton mRNA over time in culture than did the rounded cells on matrigel. We conclude that hepatocytes cultured on matrigel, as opposed to the standard collagen, exhibit remarkably enhanced expression of many liver-specific functions.

Animals↗
PubMed1988

Sex change in cytochrome P-450 phenotype by growth hormone treatment of adult rat hepatocytes maintained in a culture system on matrigel.

Results of studies of hypophysectomized rats suggest that growth hormone serves as a final common mediator through which gonadal steroids and other modifiers of pituitary function alter the expression of gender-specific liver genes such as the sexually dimorphic pair of cytochrome P-450 isozymes, male-specific P-450h and female-specific P-450i. We tested the effects of growth hormone in a system for primary monolayer culture of adult rat hepatocytes on a laminin-rich extracellular matrix (matrigel), which permits sustained expression of both constitutive and inducible liver genes in a chemically defined medium. Cultures of freshly isolated hepatocytes prepared from untreated male rats and samples of the intact donor liver contained readily detectable quantities of immunoreactive P-450h protein (measured on immunoblots of cell microsomes) and P-450h mRNA (measured on Northern blots of cellular RNA). Neither P-450i immunoreactive protein nor P-450i mRNA were present. Addition of physiologic concentrations of human or bovine growth hormone, but not of prolactin, to culture medium lacking insulin or other hormones resulted in prompt induction of P-450i immunoreactive protein and P-450i mRNA. Induction of P-450i mRNA in male hepatocyte cultures was dependent on the concentration of growth hormone, required as little as 24 hr of exposure, and was markedly attenuated in cultures maintained on type I collagen rather than on matrigel. Growth hormone treatment also induced the level of mRNA for insulin-like growth factor I, whereas the amount of mRNA for the male-specific urinary protein alpha 2 mu-globulin was unaffected. Cultures of hepatocytes derived from untreated adult female rats retained high levels of P-450i mRNA but only if the culture medium contained growth hormone. None of the tested treatments with estrogens, androgens, glucocorticoids, or growth hormone induced P-450h mRNA or P-450h immunoreactive protein in cultures of female hepatocytes. We conclude that the somatogenic effects of growth hormone acting alone and directly on the hepatocyte in culture are sufficient to "feminize" the cytochrome P-450 phenotype. The present culture system offers a way to explore the molecular basis for hormonal control of liver gene expression.

Animals↗
PubMed1988

A comparison between different types of covalent DNA modifications (I-compounds, persistent carcinogen adducts and 5-methylcytosine) in regenerating rat liver.

I-Compounds have been recently identified as adduct-like nonpolar covalent DNA modifications that are detectable by 32P-postlabeling assay in tissues of untreated experimental animals and increase with age. Additional I-compounds have now been observed in liver DNA of male Sprague-Dawley rats when the chromatographic conditions were modified to allow for the detection of more polar adducts exhibiting low affinity to polyethyleneimine (PEI)--cellulose anion-exchange thin-layer material. The total I-compound level in 10-month-old animals was as high as one modification in approximately 10(7) nucleotides. This represented a minimum estimate since 100% recovery of all rat liver I-compounds in 32P-labeled form presumably was not achieved by the procedures used. The I-compound pattern was reproducible and variation of I-compound levels among individual animals of the same age was small. We have used regenerating rat liver herein as a model to compare the properties of I-compounds with those of persistent 2-acetylaminofluorene (AAF)-induced DNA adducts and of 5-methylcytosine (m5C), a normal enzymatic DNA modification. Eight- to 10-month-old male Sprague-Dawley rats were given 2-AAF (50 mg/kg in DMSO) or vehicle (DMSO) by i.p. injection. Partial hepatectomy was performed 6 weeks later (i.e. after AAF adduct levels had stabilized) and regenerating liver samples were taken 1 week after the operation for DNA analysis. Consistent with the restoration of cell and tissue loss, the overall levels of I-compounds and 2-AAF adducts were reduced to approximately 47% and approximately 45% respectively of control in regenerating liver by dilution with newly synthesized DNA, while the m5C level was not affected. Thus, in regenerating liver, I-compounds resembled carcinogen--DNA adducts and not m5C. This supports our hypothesis that the formation of these DNA modifications may be due to the binding to DNA of small amounts of reactive electrophilic by-products of normal metabolic activities, leading to the slow accumulation of I-compounds in tissue DNA with ageing.

2-Acetylaminofluorene↗