Biomedical subjects

W Zheng

Publications and source records attributed to W Zheng.

At least 55 records · Page 3Linked to original sources

PubMed2001

Resolving the structure of ionized helium in the intergalactic medium with the far ultraviolet spectroscopic explorer.

The neutral hydrogen (H I) and ionized helium (He II) absorption in the spectra of quasars are unique probes of structure in the early universe. We present Far-Ultraviolet Spectroscopic Explorer observations of the line of sight to the quasar HE2347-4342 in the 1000 to 1187 angstrom band at a resolving power of 15,000. We resolve the He II Lyman alpha (Lyalpha) absorption as a discrete forest of absorption lines in the redshift range 2.3 to 2.7. About 50 percent of these features have H I counterparts with column densities N(H I) > 10(12.3) per square centimeter that account for most of the observed opacity in He II Lyalpha. The He II to H I column density ratio ranges from 1 to >1000, with an average of approximately 80. Ratios of <100 are consistent with photoionization of the absorbing gas by a hard ionizing spectrum resulting from the integrated light of quasars, but ratios of >100 in many locations indicate additional contributions from starburst galaxies or heavily filtered quasar radiation. The presence of He II Lyalpha absorbers with no H I counterparts indicates that structure is present even in low-density regions, consistent with theoretical predictions of structure formation through gravitational instability.

Journal Article↗

PubMed2001

Population-based case-control study of soyfood intake and breast cancer risk in Shanghai.

We evaluated the association of soyfood intake and breast cancer risk in a population-based case-control study among Chinese women in Shanghai. Included in the study were 1459 cases and 1556 age-matched controls, with respective response rates of 91.1% and 90.3%. Usual soyfood intake was assessed using a food frequency questionnaire (FFQ). Separate analyses were performed for all subjects and for the subset who reported no recent change in soyfood intake. The intake levels of soyfoods among women in Shanghai are high, with 96.6% women reporting soyfood consumption at least once a week. A statistically non-significant reduced risk (odds ratio (OR) = 0.78 95% CI = 0.52-1.16) of breast cancer was observed among those who reported eating soyfood at least once a week. Compared to those in the lowest decile intake group, women in the highest decile intake group had a 30% reduced risk of breast cancer (OR = 0.66, 95% CI = 0.46-0.95), but no monotonic dose-response relation was observed (P for trend, 0.28). Stratified analyses showed that the inverse association was restricted primarily among women who had a high body mass index (BMI), with an adjusted OR of 0.30 (95% CI = 0.10-0.94) observed for the highest intake group. The reduction in risk was stronger for breast cancer positive for both oestrogen receptor (ER) and progesterone receptor (PR) (OR = 0.44, 95% CI = 0.25-0.78) than those with other ER/PR status. More pronounced inverse associations were observed in analyses among those who reported no recent change in soyfood intake than those conducted in all subjects. A dose-response relation between soyfood intake and breast cancer risk was observed in this subset of women (P for trend, 0.02), with an OR of 0.46 (95%CI = 0.28-0.75) for those in the highest decile intake group. No clear monotonic dose-response relation was found between soyfood intake and breast cancer risk among regular soy eaters, but nevertheless the results suggest that regular soyfood consumption may reduce the risk of breast cancer, particularly for those positive for ER and PR; the effect may be modified by body mass index.

Body Constitution↗

PubMed2001

[Clinical characteristics and treatment of midline nasal and nasal type NK/T cell lymphoma].

OBJECTIVE: To study the clinical characteristics and treatment of midline nasal and nasal type T/Nk cell non-Hodgkin lymphoma. METHODS: A retrospective study was made on the clinical characteristics, treatment, short-term effect, and two-year survival rate of 37 patients with midline nasal and nasal type T/NK non-Hodgkin lymphoma. RESULTS: All of the patients were primarily treated with 2 cycles of CHOP chemotherapy. Ten of them were with good effect (common group). Then they were given 6 cycles of chemotherapy followed by focal radiotherapy and reached complete remission (CM). The other 27 patients failed to reach partial remission (PM) or even with their condition worsened after 2 cycles of CHOP regimen and were included into the refractory group. Fourteen of them received L-asparaginase-based salvage chemotherapy followed by focal radiotherapy (L-ASP group), and salvage therapy without L-ASP and followed by focal radiotherapy was given to the other 13 patients (non-L-ASP group). Continuous fever, angioinvasive growth and necrotic lesion could not be found among the patients in the common group. Their international prognostic indexes (IPI) were 0 approximately 1. Seventy percent of them were at the stages I or II. Continuous fever, angioinvasive growth and necrotic lesion could be found in the patients in refractory group. The IPIs among 85% of them were > 2, and 82% of them were at the stages III and IV. The CR rate was 46% for all patients as a whole, 100% for the common group, 26% for the refractory group (P < 0.005); and was 50% for the L-ASP group and 0% for the non-L-ASP group (P < 0.005). The 2-year survival rate was 43% for all patients as a whole, 100% for the common group, 20% for the refractory group (P < 0.005); and was 50.8% for the L-ASP group and 0% for the non-L-ASP group (P < 0.005). CONCLUSION: Patients with midline nasal and nasal type T/NK non-Hodgkin lymphoma can be treated primarily by CHOP regimen and local radiotherapy. Refractory patients can be treated by salvage therapy based on L-ASP chemotherapy with a rather good effect. The clinical characteristics of most of the refractory patients include continuous fever, angioinvasive growth, necrotic lesion, being at stage III and IV, and with an IPI > 2.

Adolescent↗

PubMed2001

Abortion history and breast cancer risk: results from the Shanghai Breast Cancer Study.

Studies of the association between induced abortion and breast cancer risk have been inconsistent, perhaps due to underreporting of abortions. Induced abortion is a well-accepted family planning procedure in China, and women who have several induced abortions do not feel stigmatized. The authors used data from a population-based case-control study of breast cancer among women age 25-64 conducted between 1996 and 1998 in urban Shanghai to assess whether a history of and the number of induced abortions were related to breast cancer risk. In-person interviews were completed with 1,459 incident breast cancer cases ascertained through a population-based cancer registry, and 1,556 controls randomly selected from the general population in Shanghai (with respective response rates of 91% and 90%). After adjusting for confounding, there was no relation between ever having had an induced abortion and breast cancer (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.7-1.2). Women who had 3 or more induced abortions were not at increased risk of premenopausal breast cancer (OR = 0.9, 95% CI 0.6-1.4) or postmenopausal breast cancer (OR = 1.3, 95% CI 0.8-2.3). These results suggest that a history of several induced abortions has little influence on breast cancer risk in Chinese women.

Abortion, Induced↗

PubMed2001

Gabaergic inhibition antagonizes adaptive adjustment of the owl's auditory space map during the initial phase of plasticity.

We studied the influence of GABA-mediated inhibition on adaptive adjustment of the owl's auditory space map during the initial phase of plasticity. Plasticity of the auditory space map was induced by subjecting owls to a chronic prismatic displacement of the visual field. In the initial stages of plasticity, inhibition suppressed responses to behaviorally appropriate, newly functional excitatory inputs. As a result, adaptive changes in excitatory input were only partially expressed as postsynaptic spike activity. This masking effect of inhibition on map plasticity did not depend on the activity of NMDA receptors at the synapses that supported the newly learned responses. On the basis of these results, we propose that the pattern of feedforward inhibition is less dynamic than the pattern of feedforward excitation at the site of plasticity. As a result, initially in the adjustment process the preexisting pattern of feedforward GABAergic inhibition opposes changes in the auditory space map and tends to preserve the established response properties of the network. The implications of this novel role of inhibition for the functional plasticity of the brain are discussed.

2-Amino-5-phosphonovalerate↗

PubMed2001

Vascular endothelial growth factor and basic fibroblast growth factor differentially modulate early postnatal coronary angiogenesis.

The roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF [FGF-2]) in early postnatal regulation of coronary angiogenesis were investigated by administering neutralizing antibodies to these growth factors between postnatal days 5 and 12. Immunohistochemistry and Western blotting both revealed decreases in VEGF protein in the hearts of rats treated with either antibody. In contrast, bFGF mRNA increased in both treated groups, whereas VEGF mRNA was unchanged. Using stereological assessment of perfusion-fixed hearts, we found that both anti-VEGF and anti-bFGF inhibited the rapid and marked capillary growth that occurs during this time period and that the effects of the two neutralizing antibodies are not additive. Arteriolar growth, as indicated by a lower length density, was inhibited by anti-bFGF, but not anti-VEGF. When both anti-VEGF and anti-bFGF were administered, arteriolar length density was not significantly lower, but the population of small arterioles (<15 microm) was markedly reduced, whereas the percentage of large arterioles (26 to 50 microm) more than doubled. Thus, inhibition of both growth factors negated or limited the formation of small arterioles and facilitated an expansion of the largest arterioles. These in vivo data are the first to document that during the early neonatal period, (1) both VEGF and bFGF modulate capillary growth, (2) bFGF facilitates arteriolar growth, and (3) the two growth factors interact to establish the normal hierarchy of the arteriolar tree.

Animals↗

PubMed2001

Syntheses and characterization of mu,eta(1),eta(1)-3,5-di-tert-butylpyrazolato derivatives of aluminum.

The 3,5-di-tert-butylpyrazolato (3,5-tBu(2)pz) derivatives of aluminum [(eta(1),eta(1)-3,5-tBu(2)pz)(mu-Al)R(1)R(2)](2) (R(1) = R(2) = Me 1; R(1) = R(2) = Et, 2; R(1) = R(2) = Cl, 3; R(1) = R(2) = I, 4; [(eta(2)-3,5-tBu(2)pz)(3)Al], 5; [Al(2)(eta(1),eta(1)-3,5-tBu(2)pz)(2)(mu-E)(C triple bond CPh)(2)] (E = S (6), Se (7), Te (8)) have been prepared in good yield. Compounds 1 and 2 were obtained by the reactions of H[3,5-tBu(2)pz] with Me(3)Al and Et(3)Al, respectively. Reaction of [(eta(1),eta(1)-3,5-tBu(2)pz)(mu-Al)H(2)](2) with the pyrazole H[3,5-tBu(2)pz] gave [(eta(2)-3,5-tBu(2)pz)(3)Al] (5). The reaction of [(eta(1),eta(1)-3,5-tBu(2)pz)(mu-Al)R(2)](2) (R = H, Me) and I(2) yielded 4, while the reaction of 1 equiv of K[3,5-tBu(2)pz] and AlCl(3) afforded 3. In addition, the reaction of [Al(2)(eta(1),eta(1)-3,5-tBu(2)pz)(2)(mu-E)H(2)] and HC triple bond CPh gave 6, 7, and 8. All compounds have been characterized by elemental analysis, NMR, and mass spectroscopy. The molecular structure analyses of compounds 1, 3, 6, and 7 by X-ray crystallography showed that complexes 1 and 3 are dimeric with two eta(1),eta(1)-pyrazolato groups in twisted conformation while 6 and 7 with two eta(1),eta(1)-pyrazolato groups display a boat conformation.

Journal Article↗

PubMed2001

2-Arylindole-3-acetamides: FPP-competitive inhibitors of farnesyl protein transferase.

A series of 2-arylindole-3-acetamide farnesyl protein transferase inhibitors has been identified. The compounds inhibit the enzyme in a farnesyl pyrophosphate-competitive manner and are selective for farnesyl protein transferase over the related enzyme geranylgeranyltransferase-I. A representative member of this series of inhibitors demonstrates equal effectiveness against HDJ-2 and K-Ras farnesylation in a cell-based assay when geranylgeranylation is suppressed.

Alkyl and Aryl Transferases↗

PubMed2001

Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells.

Our previous studies show that manganese (Mn) exposure inhibits aconitase, an enzyme regulating the proteins responsible for cellular iron (Fe) equilibrium. This study was performed to investigate whether Mn intoxication leads to an altered cellular Fe homeostasis in cultured neuronal or neuroglial cells as a result of disrupted Fe regulation. Our results reveal a significant increase in the expression of transferrin receptor (TfR) mRNAs and a corresponding increase in cellular 59Fe net uptake by PC12 cells, but not astrocytes, following Mn exposure. These findings suggest that alteration by Mn of cellular Fe homeostasis may contribute to Mn-induced neuronal cytotoxicity.

Animals↗

PubMed2001

Lifetime physical activity and breast cancer risk in the Shanghai Breast Cancer Study.

Overall physical activity in adolescence and adulthood, and changes in activity over the lifespan were analysed by in-person interviews among 1459 women newly diagnosed with breast cancer and 1556 age-matched controls in urban Shanghai. Physical activity from exercise and sports, household, and transportation (walking and cycling) was assessed in adolescence (13-19 y) and adulthood (last 10 y), as was lifetime occupational activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence limits (OR (95% CL)) while controlling for confounders. Risk was reduced for exercise only in adolescence (OR = 0.84 (0.70-1.00)); exercise only in adulthood (OR = 0.68 (0.53-0.88)), and was further reduced for exercise in both adolescence and adulthood (OR = 0.47 (0.36-0.62)). Graded reductions in risk were noted with increasing years of exercise participation (OR(1-5 yrs)= 0.81 (0.67-0.94); OR(6-10 yrs)= 0.74 (0.59-0.93); OR(11-15 yrs)= 0.55 (0.38-0.79); OR(16 + yrs)= 0.40 (0.27-0.60);P(trend,)< 0.01). Lifetime occupational activity also was inversely related to risk (P(trend)< 0.01). These findings demonstrate that consistently high activity levels throughout life reduce breast cancer risk. Furthermore, they suggest that women may reduce their risk by increasing their activity levels in adulthood.

Adolescent↗

PubMed2001

Mutations in DnaA protein suppress the growth arrest of acidic phospholipid-deficient Escherichia coli cells.

Cell growth arrests when the concentrations of anionic phospholipids drop below a critical level in Escherichia coli, with the insufficient amounts of acidic phospholipids adversely affecting the DnaA-dependent initiation of DNA replication at the chromosomal origin (oriC). Mutations have been introduced into the carboxyl region of DnaA, including the portion identified as essential for productive in vitro DnaA-acidic phospholipid interactions. Expression of DnaA proteins possessing certain small deletions or substituted amino acids restored growth to cells deficient in acidic phospholipids, whereas expression of wild-type DnaA did not. The mutations include substitutions and deletions in the phospholipid-interacting domain as well as some small deletions in the DNA-binding domain of DnaA. Marker frequency analysis indicated that initiation of replication occurs at or near oriC in acidic phospholipid- deficient cells rescued by the expression of DnaA having a point mutation in the membrane-binding domain, DnaA(L366K). Flow cytometry revealed that expression in wild-type cells of plasmid-borne DnaA(L366K) and DnaA(Delta363-367) reduced the frequency with which replication was initiated and disturbed the synchrony of initiations.

Amino Acid Substitution↗

PubMed2001

In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B.

Halichondrin B is a highly potent anticancer agent originally found in marine sponges. Although scarcity of the natural product has hampered efforts to develop halichondrin B as a new anticancer drug, the existence of a complete synthetic route has allowed synthesis of structurally simpler analogues that retain the remarkable potency of the parent compound. In this study, we show that two macrocyclic ketone analogues of halichondrir B, ER-076349 and ER-086526, have sub-nM growth inhibitory activities in vitro against numerous human cancer cell lines as well as marked in vivo activities at 0.1-1 mg/kg against four human xenografts: MDA-MB-435 breast cancer, COLO 205 colon cancer, LOX melanoma, and NIH: OVCAR-3 ovarian cancer. ER-076349 and ER-086526 induce G2-M cell cycle arrest and disruption of mitotic spindles, consistent with the tubulin-based antimitotic mechanism of halichondrin B. This is supported further by direct binding of the biotinylated analogue ER-040798 to tubulin and inhibition of tubulin polymerization in vitro by ER-076349 and ER-086526. Retention of the extraordinary in vitro and in vivo activity off halichondrin B in structurally simplified, fully synthetic analogues establishes the feasibility of developing halichondrin B-based agents as highly effective, novel anticancer drugs.

Animals↗

PubMed2001

Toxicology of choroid plexus: special reference to metal-induced neurotoxicities.

The chemical stability in the brain underlies normal human thinking, learning, and behavior. Compelling evidence demonstrates a definite capacity of the choroid plexus in sequestering toxic heavy metal and metalloid ions. As the integrity of blood-brain and blood-CSF barriers, both structurally and functionally, is essential to brain chemical stability, the role of the choroid plexus in metal-induced neurotoxicities has become an important, yet under-investigated research area in neurotoxicology. Metals acting on the choroid plexus can be categorized into three major groups. A general choroid plexus toxicant can directly damage the choroid plexus structure such as mercury and cadmium. A selective choroid plexus toxicant may impair specific plexus regulatory pathways that are critical to brain development and function, rather than induce massive pathological alteration. The typical examples in this category include lead-induced alteration in transthyretin production and secretion as well as manganese interaction with iron in the choroid plexus. Furthermore, a sequestered choroid plexus toxicant, such as iron, silver, or gold, may be sequestered by the choroid plexus as an essential CNS defense mechanism. Our current knowledge on the toxicological aspect of choroid plexus research is still incomplete. Thus, the future research needs have been suggested to focus on the role of choroid plexus in early CNS development as affected by metal sequestration in this tissue, to explore how metal accumulation alters the capacity of the choroid plexus in regulation of certain essential elements involved in the etiology of neurodegenerative diseases, and to better understand the blood-CSF barrier as a defense mechanism in overall CNS function.

Animals↗

PubMed2001

Multiple growth factors regulate coronary embryonic vasculogenesis.

Mechanisms regulating coronary vascularization are not well understood. To test hypotheses regarding the influence of key growth factors and their interactions, we studied vascular tube formation (vasculogenesis) in collagen gels onto which quail embryonic ventricles were placed and incubated in the presence of growth factors or inhibitors. Vasculogenesis in this model is dependent on tyrosine kinase receptors, since tube formation was totally blocked by genestein. Tube formation was attenuated when anti-bFGF or anti-VEGF neutralizing antibodies were added to the medium and nearly completely inhibited when the both were added. The attenuation associated with anti-VEGF was due primarily to a decrease in assembly of endothelial cells, while that associated with bFGF was primarily due to a reduction in endothelial cells. Soluble tie-2, the receptor for angiopoietins, also had an inhibitory effect and, when added with either anti-bFGF or anti-VEGF, markedly attenuated tube formation. At optimal doses, tube formation was enhanced 6.5-fold by bFGF and 2.5-fold by VEGF over the controls. Each of these growth factors was dependent upon the other for optimal induction of tube formation, since neutralizing antibodies to one markedly reduced the potency of the other. VEGF potency was also markedly reduced when soluble tie-2 was added to the medium. Tube formation was virtually totally blocked by exogenous TGF-beta at doses > 1 ng/ml, while neutralizing TGF-beta antibodies enhanced tube formation 2-fold in the 30 ng-30 microg range. These data provide the first documentation of multiple growth factor regulation of coronary tube formation.

Animals↗

PubMed2001

Miniaturization of a hepatitis C virus RNA polymerase assay using a -102 degrees C cooled CCD camera-based imaging system.

Innovations in detection technologies have allowed us to develop a novel assay in 1536-well plate format and assess the advantages of screen miniaturization compared with conventional high-throughput compound screening in 96- or 384-well plates. An HCV RNA polymerase assay has been miniaturized in 1536-well plates by using a new detection technology known as LEADseeker homogeneous imaging system. It uses a -102 degrees C cooled charge-coupled device (CCD) camera and newly designed scintillation proximity microparticles. The miniaturized assay used europium-doped streptavidin-coated yttrium oxide (YO(x)) or polystyrene (PS) microspheres to capture biotin-labeled [(3)H]RNA product transcripts. Beads in proximity to the radioisotope convert the emitted beta(-) particles into photons having wavelengths in the red region of the visible spectrum, optimal for detection by the CCD camera. Because the camera collects light from all wells of the plate simultaneously, 1536-well plates are imaged as rapidly as 384-well plates, on the order of 10 min per plate. The assay has a signal to background of approximately 20-fold, satisfactory for high-throughput robotics screening. The enzyme kinetics and potency of a known inhibitor were similar to those obtained from the conventional assay using scintillation proximity assay (SPA) beads and a scintillation plate counter. Furthermore, the newly developed microbeads (emitting at 610 to 620 nm) are less prone to quenching effects caused by yellow-colored compounds, than conventional SPA beads or scintillation fluid (emitting at 400 to 480 nm region). Thus, the LEADseeker imaging system is a useful new tool for miniaturization of assays for high-throughput screening.

Cold Temperature↗

PubMed2001

A Cre-expressing cell line and an E1/E2a double-deleted virus for preparation of helper-dependent adenovirus vector.

Adenoviral vectors are attractive for the delivery of transgenes into mammalian cells because of their efficient transduction, high titer, and stability. The major concerns with using E1-deleted adenoviral vectors in gene therapy are the pathogenic potential of the virus backbone and the leaky viral protein synthesis that leads to host immune responses and a short duration of transgene expression. Helper-dependent (HD) adenoviral vectors that are devoid of all viral protein-coding sequences have significantly increased the safety and reduced the immunogenicity of these vectors. Currently available HD vectors depend on an E1-deleted adenovirus as a helper to provide viral proteins in trans. As a consequence, contamination with helper virus cannot be avoided in the HD vector preparation though it can be decreased to 0.01% using a Cre/loxP mechanism. Since the presence of E1-deleted helper virus may have substantial unwanted effects, we have developed a new Cre-expressing cell line based on an E1- and E2a-complementing cell. This new cell line can efficiently cleave the packaging region in the helper virus genome. We have also developed an E1 and E2a double-deleted helper virus. By using the CreE cell with the helper virus deleted in both the E1 and the E2a genes it may be possible to further improve the safety of the vectors.

Adenoviridae↗

PubMed2001

Stem cells in neurodevelopment and plasticity.

The processes of stem cell proliferation and differentiation during embryogenesis are governed by transcription factors that regulate the regional differentiation of the central nervous system (CNS). Do neural "stem" cells persisting in the postnatal CNS disobey this sequence of events? The division of neural progenitor cells is promoted by basic Fibroblast Growth Factor Fgf2 or Epidermal Growth Factor Egf. However, while the intraventricular administration of FgF2 during embryogenesis increases the generation of cortical pyramidal neurons, the same treatment in the adult CNS produces interneurons of the olfactory bulb. The competence of neural progenitor cells to respond to Fgf is dictated by nuclear transcription factors that constrain neuronal fates through time. Developmentally regulated transcriptional programs are regulated by cell interactions, as dividing cells check their molecular signature against that of their environment. Thus, cell surface interactions account for competitive phenomena among pools of cells, including the inhibitory effect of neurons on the division of their progenitors, and may also explain the "permissive" effects of non-CNS environments. The challenge remains to understand the genetic programs that control the fate of progenitor cells within the postnatal CNS and their regulation by stress, apoptosis and environmental perturbations. These programs are likely to be similar to gene cascades that control proliferation, differentiation and migration of progenitor cells at earlier stages of development.

Animals↗

PubMed2001

Mechanistic studies on the alkyltransferase activity of serotonin N-acetyltransferase.

BACKGROUND: Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) catalyzes the first, rate-limiting step in the biosynthesis of the circadian hormone melatonin (5-methoxy-N-acetyltryptamine) from serotonin. Our recent discovery that, in addition to catalyzing the acetyl transfer from acetyl-coenzyme A (acetyl-CoASH) to serotonin, AANAT is also a robust catalyst for the alkyl transfer reaction between CoASH and N-bromoacetyltryptamine has not only opened up a new way to develop cell-permeable AANAT acetyltransferase inhibitors that are valuable in vivo tools in helping elucidate melatonin's (patho)physiological roles, but has also raised a question - how does AANAT accelerate the alkyl transfer reaction? In this study, mechanistic aspects of the AANAT-catalyzed alkyl transfer reaction were explored by employing CoASH and a series of N-haloacetyltryptamines that were also evaluated for their AANAT acetyltransferase inhibitory activities. RESULTS: Investigation of various N-haloacetyltryptamine analogs showed a similar leaving group effect on the enzymatic and non-enzymatic reaction rates. Steady-state kinetic analyses demonstrated that AANAT alkyltransferase obeys a sequential, ternary complex mechanism, with random substrate binding. Rate versus pH profiles revealed the catalytic importance of an ionizable group with pK(a) of approximately 7. All those N-haloacetyltryptamines that serve as substrates of AANAT alkyltransferase are also potent (low micromolar) in vitro inhibitors against AANAT acetyltransferase activity. In particular, N-chloroacetyltryptamine was also shown to be a potent inhibitor of intracellular melatonin production in a pineal cell culture assay. CONCLUSIONS: This is the first detailed investigation of the alkyltransferase activity associated with an acetyltransferase. Our results indicate that AANAT does not accelerate the alkyl transfer reaction by simple approximation effect as previously proposed for the similar alkyl transfer reaction catalyzed by other acyltransferases. This study has general implications for developing novel inhibitors by taking advantage of the promiscuous alkyltransferase activity associated with several acyltransferases.

Alkyl and Aryl Transferases↗