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Nine DNA fragments of HIV-1 env gene were amplified by PCR from uncultured peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 sero-positive intravenous drug users (IDUs) in Sichuan province, in mid 1996. Their C2-V3 region (about 450 bp) was sequenced. Sequence analysis showed that there were two HIV-1 subtypes B and C, with 1.4% and 2.6% gene divergence inside each subtype, in Sichuan. The 5 subtype B strains, when comparing with sequences of several reference HIV-1 strains, were found similar to these identified in Thailand, Myanma and Yunnan province. The nucleotide sequence divergence between them was ranged from 3.6% to 4.3%. Meanwhile, the 4 subtype C strains except sc3, were most close to those found in India as well as in Yunnan province, and both their nucleotide sequence divergence was 3.1%. The sc3 strain belonged to subtype C but had larger genetic distance, between 10.1%-17.2%. Above results suggested a recent epidemic of both subtype HIV-1 strains in Sichuan provine and they were very close to those identified in Yunnan province: The subtype C strain of sc3 is special and its source remains not clear.

In order to help assess the risk to astronauts due to the long-term exposure to the natural radiation environment in space, an understanding of how the primary radiation field is changed when passing through shielding and tissue materials must be obtained. One important aspect of the change in the primary radiation field after passing through shielding materials is the production of secondary particles from the breakup of the primary. Neutrons are an important component of the secondary particle field due to their relatively high biological weighting factors, and due to their relative abundance, especially behind thick shielding scenarios. Because of the complexity of the problem, the estimation of the risk from exposure to the secondary neutron field must be handled using calculational techniques. However, those calculations will need an extensive set of neutron cross section and thicktarget neutron yield data in order to make an accurate assessment of the risk. In this paper we briefly survey the existing neutron-production data sets that are applicable to the space radiation transport problem, and we point out how neutron production from protons is different than neutron production from heavy ions. We also make comparisons of one the heavy-ion data sets with Boltzmann-Uehling-Uhlenbeck (BUU) calculations.

A method for the separation and determination of avermictin in avermictin tablet by reversed-phase high performance liquid chromatography (RP-HPLC) was developed. Operating conditions were as follows: TSK-GEL C18 column, 250 mm x 4.6 mm i.d., MeOH-H2O (75:25, V/V) mobile phase with a flow rate of 1.0 mL/min, and UV detection at 245 nm. The results showed that the active constituents avermictin B1a and B1b can by separated effectively. The relative standard deviations were 2.56% and 1.31%, respectively (n = 6). The method is accurate, rapid and simple, and provides a scientific basis for industrial production and quality control of avermictin tablet.

Acute myeloid leukemia (AML) is the most common form of acute leukemia. Contemporary chemotherapy regimens fail to cure most patients with AML. We have genetically engineered a recombinant diphtheria toxin human granulocyte macrophage colony-stimulating factor (GMCSF) chimeric fusion protein (DTctGMCSF) that specifically targets the GMCSF receptor on fresh human AML cells and myeloid leukemia cell lines. At a nontoxic dose level, DTctGMCSF therapy was superior to the standard chemotherapeutic agents 1-beta-D-arabinofuranosylcytosine and Adriamycin, resulting in 60% long-term event-free survival of severe combined immunodeficient mice challenged with an otherwise invariably fatal cell dose of the human HL-60 myeloid leukemia. Notably, systemic exposure levels of DTctGMCSF, which were found to be therapeutic in the severe combined immunodeficient mouse xenograft model of human HL-60 myeloid leukemia, could be achieved in cynomolgus monkeys without any significant nonhematological toxicities. The recombinant DTctGMCSF fusion toxin might be useful in the treatment of AML patients whose leukemias have recurred and developed resistance to contemporary chemotherapy programs.

We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.

We discuss the best therapeutic method for sarcoma of the breast. The data of all cases treated from March 1964 to May 1994 were analyzed retrospectively. Of all cases, 7 died, 9 recurred, and 15 survived more than 15 years and 5 over 20 years. The follow-up time was 4 months to 25 years. Most sarcomas were pathologically proved. The best therapeutic method was operation. The sarcomas of all cases must be extensively resected including surrounding tissues. The recurrent sarcoma should be resected again. The axillary lymphnodes should not be eliminated when lymphnodes is not discovered.

We examined diastolic transmitral, left atrial appendage, and pulmonary venous flow pulsed-wave Doppler velocities in five dogs sedated with Valium and ketamine both before and 1 week after rapid (400 beats/min) atrial pacing with transesophageal echocardiography. Left ventricular systolic function was assessed with long-axis fractional area shortening with the use of transesophageal echocardiography. Transmitral and left atrial appendage atrial systolic and pulmonary vein systolic velocities decreased significantly. The transmitral and left atrial appendage early-to-late velocity ratios increased significantly and the pulmonary venous systolic-to-diastolic velocity ratio decreased significantly after rapid atrial pacing. Thus, 1 week of rapid atrial pacing results in impaired global and regional atrial pump function and enhanced conduit function of the left atrium with preservation of left ventricular systolic function. These findings may have implications for anticoagulation therapy in patients with atrial arrhythmia.

The 4,639,221-base pair sequence of Escherichia coli K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.

The last step in the sequence of reactions that lead to protein splicing is the intramolecular O-N or S-N acyl rearrangement of the ester or thioester linkage, respectively, between the two exteins and hydrolysis of the aminosuccinimide residue at the C-terminus of intein. This paper presents data on the rates of O-N and S-N acyl rearrangements of two model depsipeptides as a function of pH and temperature. The rates of rearrangement of both the oxygen ester and the thioester depsipeptide increased strikingly with pH, with the thioester being about 10(3) times more reactive at pH 5.5, and had a relatively low dependence on temperature, indicative of a low activating energy. The rates of O-N and S-N acyl rearrangement of these two model depsipeptides greatly exceed the rate of protein splicing, explaining why the last step of protein splicing can occur without catalysis by the intein.

Studies in the rapid-pacing model of heart failure have shown that left ventricular (LV) systolic function normalizes on cessation of pacing and LV diastolic dysfunction persists, but there is no information regarding atrial function under these conditions. To determine the effects of cessation of pacing on left atrial (LA) systolic and diastolic function, ten dogs with rapid pacing-induced heart failure (250 beats/min for 3-4 wk), six dogs with regression of heart failure (4 wk after cessation of rapid pacing), and seven control dogs were instrumented with LA sonomicrometers and micromanometers. At matched LA pressure, LA ejection (10.2 +/- 3.0 vs. 17.4 +/- 5.5%), reservoir volume fractions (19 +/- 8 vs. 35 +/- 11%), and heart rate-corrected mean normalized systolic ejection rate (1.25 +/- 0.33 vs. 1.60 +/- 0.44 EF/s) were significantly less, and the volume-normalized diastolic stiffness constant (4.9 +/- 0.8 vs. 3.2 +/- 1.1) was significantly greater, in regression versus control dogs; these changes were associated with incomplete regression of LA hypertrophy and a persistent 77.4% increase in beta-myosin heavy chain (beta-MHC) in the LA body. LV systolic function and weight were not significantly different, whereas the time constant of LV relaxation was longer (52.5 +/- 4.4 vs. 40.8 +/- 7.6 ms; P < 0.05) and LV end-diastolic pressure was greater (12.2 +/- 1.8 vs. 7.1 +/- 2.0 mmHg; P < 0.05) in regression compared with control dogs. Thus, unlike the normalization of LV systolic function observed with cessation of rapid pacing, LA systolic function is persistently abnormal, owing in part to persistent LV diastolic dysfunction, residual LA hypertrophy, and MHC isoform switches.

A RP-HPLC method was developed to determine the concentrations of sinomenine HCl in serum and urine and its pharmacokinetics was studied in healthy volunteers. C18H37 column was eluted with the mobile phase of acetonitrile--0.01 mol.L-1 sodium phosphate monobasic--N, N, N', N'-tetramethylenediamine (46:54:0.22 v/v, pH 6.9) and the ultraviolet absorbance was monitored at 263 nm. Triazolan was used as internal standard. The calibration curves were linear in the range of 6-480 ng.ml-1 in serum and 0.06-3 micrograms.ml-1 in urine, with mean recoveries of 75.46% and 91.38% respectively. The lowest detectable limits were 4 ng.ml-1 in serum and 40 ng.ml-1 in urine and the RSD for the intra-day and inter-day were less than 5%. A single oral dose of 80 mg sinomenine HCl tablet was given to 8 healthy male volunteers. The concentrations of sinomenine HCl in serum and urine were determined. The serum concentration--time curve was found to fit a two-compartment open model with first order elimination. The pharmacokinetic parameters were: T1/2 alpha 0.791 +/- 0.491 h, T1/2 beta 9.397 +/- 2.425 h, Tmax 1.040 +/- 0.274 h, Cmax 246.604 +/- 71.165 ng.ml-1, AUC 2651.158 +/- 1039.050 ng.h.ml-1, CL 0.033 +/- 0.010 ng.ml-1.

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.

Background: Many of the cardiovascular manifestations of thyroid hormone excess resemble those produced by sympathoadrenal stimulation. The objective of this study was to determine the effects of thyroid hormone excess on myocardial beta-adrenergic expression and responsiveness to infused agonists in the primate heart., Methods and Results: The responses of left ventricular isovolumic contraction (dP/dt(max)) and relaxation (tau) during graded dobutamine infusion were studied both before and after 4 weeks of thyroid hormone administration in 8 chronically instrumented baboons. At matched (atrially paced) heart rates, thyroid hormone significantly increased resting dP/dt(max) (3073+/-1034 versus 2318+/-829 mm Hg/s, P<.05) and decreased tau (24.0+/-5.5 versus 28.2+/-5.4 ms, P<.05). The change from baseline for dP/dt(max) and tau in response to beta1-adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 microg x kg(-1) x min(-1)), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when beta2-adrenergic stimulation was produced by terbutaline infusion in three additional baboons. beta-Adrenergic receptor (betaAR) expression was higher in five thyroxine-treated than in five control baboons (37.4+/-1.2 versus 15.7+/-3.2 fmol/mg, P<.001), and this was due to a greater increase in the beta2AR (5.9+/-1.5 to 20.6+/-1.2 fmol/mg, P<.001) than the beta1AR (9.7+/-1.7 to 16.8+/-0.1 fmol/mg, P<.01) subtype., Conclusions: In the primate heart, thyroid hormone produces positive inotropic and lusitropic effects in the resting state and upregulates both beta1AR and beta2AR, with the beta2AR increase predominating. At equivalent rates, however, thyroid hormone excess does not appear to enhance the sensitivity of left ventricular contractility and relaxation to either beta1- or beta2-adrenergic stimulation.

A further investigation of Aster lingulatus has led to the isolation of two additional novel triterpene saponins, asterlingulatoside C [3-O-beta-D-glucopyranosyl-3 beta, 16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha- L- arabinopyranoside] (1) and asterlingulatoside D [3-O-beta-D-glucopyranosyl-3 beta,16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside] (2). Elucidation of the structures of 1 and 2 was mainly based on FABMS and 1D and 2D homonuclear and heteronuclear NMR techniques. Compounds 1 and 2 showed good inhibitory activity against DNA synthesis in human leukemia HL-60 cells with IC50 values of 8.8 and 6.1 microM, respectively.

To gain insight into neuronal-glial signaling in brain, cerebellar Bergmann glia and granule neurons were studied in acutely isolated slices with the aid of laser scanning confocal microscopy. Both Bergmann glia and granule neurons responded to N-methyl-D-aspartate (NMDA) with a rise in [Ca2+]i. However, the glial NMDA response was frequently inhibited by tetrodotoxin, suggesting that the response depended on neuronal action potentials, rather than on direct activation of NMDA receptors on the Bergmann glia. Further experiments demonstrated that the NMDA response in Bergmann glia was not inhibited by a combination of non-NMDA glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione and alpha-methyl-4-carboxyphenylglycine. Bergmann glia also responded to norepinephrine and high K+, and the responses were not inhibited by tetrodotoxin. The glial norepinephrine response was blocked by phentolamine but not by the removal of external Ca2+, indicating a direct activation of alpha1-adrenergic receptors that mediated release of Ca2+ from intracellular stores. The KCl-induced response in both neurons and glia was dependent on external Ca2+ and was blocked by verapamil or nifedipine. In summary, our data indicate that Bergmann glia in situ recognize a signal(s) released from neurons during neuronal activity.

Two oligofurostanosides were isolated from the seeds of Asparagus officinalis L and their structures characterized as 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-(alpha-L-rhamnopyranosyl- (1-->4))-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-(25R) -22 alpha-methoxyfurost-5-ene-3 beta,26-diol(methyl protodioscin) and its corresponding 22 alpha-hydroxy analogue (protodioscin). The structural identification was performed using detailed analysis of 1H- and 13C-NMR spectra including two-dimensional NMR spectroscopy (COSY, HMQC, NOESY and HMBC), and chemical conversions. These two compounds have been shown to inhibit the growth of human leukemia HL-60 cells in culture and macromolecular synthesis in a dose-dependent manner. The inhibitory effect on DNA synthesis was found to be irreversible.

Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.

The purpose of the present study was to evaluate whether intermittent exposure to a constant dose of doxorubicin selects for multidrug resistance (MDR) in RPMI 8226 human myeloma cells and, if so, to determine the molecular mechanism. In an attempt to approximate clinical doxorubicin treatment in vitro, cells were exposed to a fixed dose of doxorubicin for 4 d alternating with growth in drug-free medium for 17 d. An MDR subline emerged, termed 8226/DOXint5, which was 3-4-fold resistant to doxorubicin, etoposide and m-AMSA, and 1.6-fold resistant to vincristine. Sensitivity to docetaxel, melphalan and cisplatin was normal. Verapamil normalized vincristine sensitivity but had little effect on resistance to the other agents. Cellular uptake and retention of daunorubicin and vincristine were reduced by approximately 10%. The 8226/DOXint5 cells showed diminished DNA topoisomerase IIalpha expression and increased expression of the multidrug resistance protein MRP. Expression of MDR1/P-glycoprotein was not detected. Immunostaining showed 70% of the cells to over-express the lung-resistance protein LRP. This new MDR myeloma cell line may prove to be a useful model for the development of strategies to overcome low-level, multifactorial MDR, which might be a common phenomenon in clinical myeloma treated with doxorubicin.

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were specifically cytotoxic to human leukemia cell lines bearing high affinity receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not toxic to mammalian hematopoietic cell lines lacking human GMCSF (hGMCSF) receptors. In receptor positive cells, cytotoxicity can be specifically blocked by a large excess of hGMCSF, confirming that its cytotoxicity is mediated through the hGMCSF receptor. THough DTctGMCSF inhibited granulocyte-macrophage colony formation by committed myeloid progenitor cells (CFU-GM), it did not significantly affect erythroid burst formation by committed erythroid progenitor cells (BFU-E), or mixed granulocyte-erythroid-macrophage-megakaryocyte colony formation by pluripotent multilineage progenitor cells (CFU-GEMM). DTctGMCSF holds promise for the treatment of myeloid lineage malignancies, and is a useful reagent to study hematopoiesis.

While apolipoprotein E (ApoE) and beta-amyloid (A beta) co-localize in senile plaques in cortex and cerebellum in Alzheimer disease (AD), the A beta-positive, predominantly diffuse plaques in the striatum do not exhibit ApoE immunoreactivity regardless of disease duration. As astrocytes are a major source of ApoE in the brain, we investigated potential regional differences in the ability of astrocytes to produce ApoE that might affect A beta processing and the progression of AD pathology. Using antibodies to ApoE, glial fibrillary acidic protein (GFAP), and A beta, we compared the pattern of immunoreactivity in senile plaques in AD autopsy tissue with that of reactive astrocytes surrounding subacute and old infarcts in both AD and non-AD cases. We found GFAP and ApoE immunoreactivity, but not A beta label in cell bodies and processes of reactive astrocytes in zones of infarction within cerebral cortex, striatum, and cerebellum, indicating that astrocytes are capable of upregulating ApoE within these 3 regions. In contrast, while astrocytes surrounded many neocortical neuritic plaques in AD, these GFAP-positive cells failed to label with ApoE; instead. ApoE label within plaques paralleled that of A beta. As expected, neither the ApoE-negative diffuse plaques of the striatum nor the ApoE-immunopositive diffuse plaques of the cerebellum were clearly associated with GFAP-immunoreactive astrocytes. The apparent absence of ApoE label in cortical plaque-associated astrocytes may signify a regulatory mechanism affecting ApoE synthesis and secretion, influenced by binding of ApoE to fibrillar amyloid within the plaques, neuritic changes, or other factors.

Contemporary therapies for acute myeloid leukemia (AML) commonly fail to cure patients because of the emergence of drug resistance. Drug resistance in AML is multifactorial but can be associated with the overexpression of transmembrane transporter molecules, including P-glycoprotein (Pgp) or the multidrug resistance-associated protein (MRP), or associated with inactivation of the p53 tumor suppressor gene, as well as overexpression of the anti-apoptotic protein bcl-2. We are investigating if novel recombinant biotherapeutics can circumvent these resistance mechanisms to effectively treat refractory AML. To target the lethal action of diphtheria toxin (DT) to high affinity granulocyte-macrophage colony-stimulating factor (GMCSF) receptors on AML blasts, we have produced a recombinant chimeric fusion toxin, DTctGMCSF. Since DTctGMCSF enters and kills its target cells by unique mechanisms (GMCSF-receptor binding and protein synthesis inhibition) and is not similar in structure to Pgp or MRP substrates, we postulated that it would be an active agent against therapy-resistant AML. DTctGMCSF was selectively cytotoxic (IC50 1-10ng/ml) to GMCSF-receptor positive AML cells expressing the Pgp- or MRP-associated multi-drug resistant phenotypes, despite high level resistance to conventional chemotherapeutic agents. DTctGMCSF also efficiently killed AML cells deficient in p53 expression, as well as radiation-resistant AML cells and mixed lineage leukemia cells expressing high levels of bcl-2. In addition, DTctGMCSF killed > 99% of primary leukemic progenitor cells from therapy-refractory AML patients under conditions that we have previously found to not adversely affect the proliferative capacity or differentiation of pluripotent normal hematopoietic progenitor cells. DTctGMCSF may prove useful in treating myeloid leukemias that are otherwise resistant to a wide range of conventional therapies.

DNA fragments of HIV-1 env gene were amplified by nested-PCR from 17 uncultured peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 seropositive intravenous drug users (IDUs) in Ruili city of Yunnan Province. The C2-V3 region (about 450 bp) of them were sequenced. Sequence analysis showed that there exists two HIV-1 subtypes, B and C, with 5.8% and 2.2% gene divergence inside each subtype. The 12 subtype B strains, were closely related to those found in Thailand, Myanma and Ruili city of Yunnan, and the nucleotide sequence divergence between them ranged from 4.4% to 4.9%; meanwhile, the 5 subtype C strains were most close to those found in India as well as Ruili city, all with a genetic distance of 1.9%. The small divergence among Ruili HIV-1 subtype C strains suggests a recent epidemic. The analysis of V3 loop amino sequence of 12 subtype B HIV-1 reveals that V3-tip motif of 6 samples (50%) is GPGQ and that of 3 samples (25%) is GPGR. In addition, the codon of arginine (R) of all the strains is CGA instead of AGA. This result is in accordance with our previous hypothesis that there is a drift in vivo from GPGR to GPGQ motif on the tipof V3-loop of HIV-1 subtype B strain in this arm with the elapse of time.

Multiagent chemotherapy regimens fail to cure more than one-half of the patients with acute myeloid leukemia (AML) because of the emergence of dominant multidrug-resistant subclones of leukemia cells. We have developed a recombinant diphtheria toxin-human granulocyte macrophage colony-stimulating factor chimeric fusion protein (DTctGMCSF) that specifically targets GMCSF receptor-positive AML cells. This novel biotherapeutic agent induced rapid apoptotic cell death of chemotherapy-resistant AML cell lines and primary leukemic cells from treatment-refractory AML patients. Our results suggest that DTctGMCSF may be useful in the treatment of AML patients whose leukemia has recurred and developed resistance to contemporary chemotherapy programs.

An increasing number of proteins are thought to self-splice post-translationally on the level of the polypeptide, producing two separate proteins from one gene, neither of which is the protein predicted from the gene sequence. The recent elucidation of the mechanism of splicing has led to the identification of a number of post-translational protein modifications that use similar chemical pathways.

To determine the biochemical and related functional effects of the thyroid analog diiodothyroproprionic acid (DITPA) on primate myocardium, we examined, both before and after 23 days of DITPA (3.75 mg/kg): myosin heavy-chain (MHC) isoforms and sarcoplasmic reticulum (SR) calcium cycling proteins; left ventricular (LV) function; and the LV force-frequency relation in four baboons chronically instrumented with sonomicrometers and micromanometers. The force-frequency relation was measured as the response of isovolumic contraction (dP/dtmax) to incremental pacing and the critical heart rate (HRcrit) as the rate at which dP/dtmax reached its maximum. DITPA increased basal LV dPt/dtmax (3,300 +/- 378 versus 2,943 +/- 413 mm Hg/sec; p = .09), and velocity of circumferential shortening (1.13 +/- 0.30 versus 0.76 +/- 0.30 circ/sec; p < .01), decreased the basal time constant of isovolumic relaxation (24.2 +/- 1.6 versus 29.9 +/- 2.5 msec; p < .05), and increased the HRcrit (203 +/- 19 versus 168 +/- 20 bpm; p < .05), without effecting significant changes in either basal heart rate (119 +/- 14 versus 111 +/- 17 bpm) or systolic blood pressure (137 +/- 14 versus 126 +/- 8 mm Hg). Quantitative immunoblotting revealed significant decreases in both phospholamban and the ratio of phospholamban to SR Ca2+ adenosine triphosphatase in DITPA-treated animals when compared to four untreated controls. By contrast, alpha-MHC isoform was undetectable in both DITPA treated and control baboons. Thus, DITPA favorably alters the stoichiometry between the SR calcium pump and its inhibitor, phospholamban, and has positive inotropic and lusitropic effects in the normal primate left ventricle, which may be useful in the treatment of heart failure. Unlike thyroid hormone, these changes occur in the absence of detectable alpha-MHC isoform protein expression and without an increase in heart rate.

Two new triterpenoid saponins named asterlingulatosides A and B were isolated from the whole plants of Aster lingulatus. Their structures were determined by spectroscopic data and chemical transformations to be 3-O-beta-D-glucopyranosyl-3 beta,16 alpha-dihydroxyolean-12-en-28-oic acid-28-O-alpha-L-O-arabinopyranoside and 3-O-beta-D-glucopyranosyl-3 beta,16 alpha-dihydroxyolean-12-en-28-oic acid-28-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside++ +. They showed inhibitory activity on DNA synthesis in human leukaemia HL-60 cells.

We investigated the effects of dietary menhaden oil on cyclophosphamide (CP) antineoplastic activity and its protective effect against CP toxicity. We found that dietary menhaden oil (HMO, 20% menhaden oil + 5% corn oil) enhanced the CP antitumor effect at the lowest dose tested (50 mg/kg) compared with the control group (LCO, 5% corn oil). Dietary HMO and CP treatment had a significant effect on the activities of tumor and liver microsomal cytochrome P-450 (CYP) over the controls. Activity of one of the key CP activating enzymes, CYP2B1 (which is similar to human CYP2B6), was significantly enhanced in the liver and tumor by the HMO diet, which could result in the formation of more pharmacologically active CP metabolites and, therefore, increased CP antitumor response. Moreover, the HMO diet exhibited a very significant protective effect against CP acute toxicity. The activity of the CP detoxifying enzyme aldehyde dehydrogenase (ADH) was significantly increased in the liver after HMO feeding; thus the observed protective effect of HMO feeding against CP toxicity may be partially the result of induction of ADH activity in the liver. In summary, our findings suggested that dietary menhaden oil can modulate ADH and CYP activities in a manner that may alter the metabolism of CP and, therefore, improve its therapeutic index by increasing its therapeutic effect and decreasing its toxicity.

The pathogenesis of fibrosis in chronic renal allograft rejection remains unknown. Since TGF-beta 1 plays a key role in fibrogenesis, we studied a rat model of chronic allograft rejection that shows similarities to the structural lesion described in patients. We previously demonstrated an increased expression of TGF-beta 1 in human kidney biopsies with acute and chronic rejection. Recipients of renal allografts (F344-Lewis) and isografts (Lewis-Lewis) were sacrificed at 4, 8, 24 and 52 weeks. Characteristic histologic changes of chronic rejection developed in the allografts as early as four weeks and were accompanied by progressive albuminuria significant by eight weeks. Allografts showed a progressive increase in mRNA expression of TGF-beta 1 and matrix proteins during the 52 week course. Increased matrix deposition by immunofluorescence was mostly present in the interstitium and vessels early and in all kidney compartments later. The mRNA expression of plasminogen activator inhibitor, a protease inhibitor stimulated by TGF-beta 1, increased along with TGF-beta 1 and matrix proteins. These results suggest that the fibrosis of chronic renal allograft rejection is mediated, at least partly, by the dual action of TGF-beta 1 on matrix deposition and degradation.

Caffeic acid phenethyl ester (CAPE) was synthesized from caffeic acid and phenethyl alcohol (ratio 1:5) at room temperature with dicyclohexyl carbodiimide (DCC) as a condensing reagent. The yield was about 38%. CAPE was found to arrest the growth of human leukemia HL-60 cells. It also inhibits DNA, RNA and protein synthesis in HL-60 cells with IC50 of 1.0 microM, 5.0 microM and 1.5 microM, respectively.

68 Cases of early breast cancer were divided into local resection group (33 cases) and local resection plus axillary dissection group (35 cases). The 3-, 5- and 10-year survival rate of the two groups were 97.0%, 78.8%, 72.7% and 94.3%, 80.0%, 77.1% respectively; The metastasis rate of the two groups were 6.1%, 12.1%, 3.0% and 8.6%, 17.1%, 8.6% respectively; and the local recurrence rate of the two groups were 6.1%, 6.1%, 3.0%, and 5.7%, 5.7%, 2.9% respectively ( P > 0.05). The cosmetic satisfaction rate of the two groups were 60.6% and 65.7% respectively ( P > 0.05). Factors relating to cosmetic results were type of breast, operative incision, age and postoperative radiotherapy. Conservative operation for early breast cancer was safe, provided incision margin was 2 cm approximately 3 cm. In all patients mammplasty was performed after tumor resection, and contralateral breast were treated by mammominification when it was necessary.

The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dtmax was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca(2+)-cycling proteins. Steady state SR Ca(2+)-ATPase and phospholamban mRNA increased in the hyperthyroid state, and alpha-MHC mRNA appeared de novo, whereas beta-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca(2+)-ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca(2+)-ATPase. Thus, thyroid hormone increases the transcription of Ca(2+)-cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.

Protein splicing involves the excision of an internal protein segment, the intein, from a precursor protein and the concomitant ligation of the flanking N- and C-terminal regions. It occurs in mesophilic bacteria, yeast, and thermophilic archaea. The ability to control protein splicing of a thermophilic intein by temperature and pH in a foreign protein context facilitated the study of the mechanism of protein splicing in thermophiles. On the other hand, no direct studies have been done on the mechanism of protein splicing in mesophiles. We examined the splicing of a chimeric protein containing the intein of the vacuolar ATPase subunit (VMA) of Saccharomyces cerevisiae that involves cysteines rather than serines at the reaction center. The steps in the splicing process were deduced by analyzing intermediates and side products that accumulated as a result of amino acid substitutions and were found to be analogous to those occurring in thermophiles. Moreover, appropriate amino acid replacements allowed us to develop the first mesophilic in vitro protein splicing system as well as strategies for modulating the rate of protein splicing and for converting the splicing reaction to an efficient protein cleavage reaction at either splice junction.

A new triterpene saponin, shimadoside A, has been isolated from Kalimeris shimadae and its structure deduced as 3-O-beta-D-glucopyranosiduronic acid-3 beta, 16 alpha-dihydroxyolean-12-en-28-oic acid-28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1--> 4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranoside by means of spectral data, especially NMR, including COSY, HMQC, HOHAHA and ROESY techniques, and chemical degradation.

In order to study the correlation of the CD44v gene abnormal expression and splicing with the clinicopathologic features, the expression of CD44v mRNA from normal colorectal mucosa, adenomatous polypi (precancerous disease) and colorectal carcinoma was studied by RT-PCR and cDNA hybridization. The results showed that CD44v mRNA was expressed in 65 of 67 (97%) primary cancers, in 20 of 20 metastatic tumors (100%) and in 5 of 7 (71.4%) precancerous diseases, but was not expressed in all 15 normal colon mucosa specimens. Abnormally spliced, high molecular weight CD44v could be detected in 10 of 20 (50%) primary cancers and in 18 of 20 (90%) metastatic cancers. In 10 patients with high molecular weight CD44v, metastases were found in 8, while metastases were found in only 2 of 10 patients with low expression of CD44v mRNA in the primary cancers. The results suggest that the expression of CD44v is very common in colorectal carcinoma. CD44v mRNA might be an early marker of colorectal carcinoma and its high expression is suggestive of tumor metastasis.

Unlabelled: Melatonin and 21-aminosteroids (lazaroids) are potent antioxidants and may attenuate the increased membrane permeability associated with profound shock. Our purpose was to test the effect of melatonin and a lazaroid (U74389-G) on cytokine production and fluid requirements after shock., Methods: Male C3H/HeN mice, 20-25 g, were hemorrhaged via a femoral artery catheter to a mean arterial pressure of 35 +/- 5 mm Hg, which was maintained for 1 hr, and then resuscitated with shed blood and crystalloid (2x vol of shed blood). Experimental mice received melatonin at 10 or 50 mg/kg, U74389-G at 3 mg/kg, or vehicle i.v. upon resuscitation, and blood was returned at 0.1 cc/min and crystalloid at 0.05 cc/min. The percentage of total crystalloid required to reach stabilization (mean arterial pressure remaining within 2 mm Hg for 5 min) was recorded. Animals were sacrificed at 1 hr postshock. Serum and anti-CD3-stimulated splenocyte culture supernatants were assayed for interleukin-6 (IL-6) and gamma-IFN by ELISA., Results: Mice receiving lazaroid or melatonin (50 mg/kg) required significantly less fluid to reach stabilization, with lazaroid-treated animals requiring 24 +/- 1% and melatonin-treated animals requiring 28 +/- 2% of total crystalloid compared to 40 +/- 3% for untreated animals. Melatonin-treated mice (50 mg/kg) had lower serum IL-6 levels (368 +/- 154 vs 1078 +/- 146 pg/ml) and lazaroid-treated mice had lower gamma-IFN levels (7 +/- 6 vs 52 +/- 15 pg/ml) compared to those of the untreated group (P < 0.05). There were no differences in splenocyte cytokine production., Conclusions: Treatment with lazaroid and melatonin both reduced postshock fluid requirements. Melatonin reduced serum IL-6 levels, while lazaroid reduced serum gamma-IFN levels, suggesting different mechanisms of action.

The crude saponins from the shoots (edible part of asparagus) of asparagus (asparagus crude saponins; ACS) were found to have antitumor activity. The ACS inhibited the growth of human leukemia HL-60 cells in culture and macromolecular synthesis in a dose and time dependent manner. The ACS at 75-100 micrograms/ml range was cytostatic. ACS concentrations greater than 200 micrograms/ml were cytocidal to HL-60 cells. The ACS at 6 and 50 micrograms/ml inhibited the synthesis of DNA, RNA and protein in HL-60 cells by 41, 5, and 4, respectively, or by 84, 68 and 59%, respectively. The inhibitory effect of ACS on DNA synthesis was irreversible.

We have finished a retrospective study of 218 premenopausal patients who underwent primary surgery for operable breast carcinoma between March 1958 and December 1984. All these patients had available records of menstrual data and had been followed-up for more than 10 years. U-nivariate analysis showed that the menstrual timing of operation, as other known prognostic factors (tumor size, node status, histological grade, TNM classification, adjuvent systemic therapy, etc), had an influence on the patients' outcome. Multivariate analysis by Cox regression model indicated that disease-free rate and overall survival rate of patients operated during the periovulatory phase (days 7-20, 123 cases) were significantly superior to those during the perimenstrual phase (days 1-6 and 21-40, 95 cases) (P < 0.01). There were no significant differences in prognosis between patients who received their operations during the follicular phase (days 4-14, 96 cases) and those during the luteal phases (days 15-40, 122 cases) (P > 0.1). We suggest that the adequate timing of operation should be further determined by prospective, randomized clinical study.

A new phenolic glycoside, asterbatanoside A [p-hydroxyacetophenone-4-O-beta-D-xylopyranosyl-(1-->6)-beta-D- glucopyranoside], and two new triterpenoid saponins, asterbatanoside B [2 alpha,3 beta,23-trihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside] and asterbatanoside C [3-O-beta-D-glucopyranosyl-2 beta,3 beta,23-trihydroxyolean- 12-en-28-oic acid-28-O-beta-D-glucopyranoside] were isolated from the roots of Aster batangensis. Their structures were determined by spectroscopic methods and chemical evidence. The total synthesis of asterbatanoside A is also reported.

Protein splicing involves the self-catalyzed formation of a branched intermediate, which then resolves into the excised intervening sequence and the spliced protein. A possible mechanism for branched intermediate formation is an N-O rearrangement of the peptide bond involving the amino group of the conserved serine/cysteine residue at the upstream splice junction to yield a linear peptide ester intermediate. This possibility was examined in using an in vitro splicing system involving the intervening sequence from the DNA polymerase of the extremely thermophilic archeon, Pyrococcus sp. GB-D. Because thioesters react much more rapidly with nitrogen nucleophiles at neutral pH than do oxygen esters, protein-splicing precursors in which the serine residue of interest was replaced by cysteine were constructed and purified. In the presence of 0.25 M hydroxylamine or 0.1 M ethylene diamine at pH 6 or higher, these constructs underwent rapid cleavage at the upstream splice junction, consistent with the aminolysis of a thioester. The site of hydroxylaminolysis was identified by analysis of the C-terminus of the polypeptide cleavage products. Comparison of the C-terminal peptide hydroxamate with the synthetic peptide hydroxamates with respect to chromatographic mobility, colorimetric assay, amino acid composition, and high-resolution mass spectrometry showed that the hydroxylamine-sensitive site in the splicing precursor was the peptide bond adjacent to the serine residue at the upstream splice junction. These results provide evidence that the peptide bond at the upstream splice junction can undergo a self-catalyzed N-O or N-S acyl rearrangement to yield a linear polypeptide ester intermediate and suggest that this kind of rearrangement constitutes the first step in protein splicing.

Asterinin D and E, pentapeptides, have been isolated from the roots of Aster tataricus L.f. (Compositae, syn. Asteraceae, subtribe Asteroideae) and their structures have been elucidated on the basis of spectroscopic analysis, as well as chemical and enzymatic methods.

In the present investigation, the behavior of learning and memory of 1-month and 6-month-old mice was studied by using Y-maze and one-trial passive avoidance response device. The synaptosomal free [Ca2+]i of four main brain regions (Hippocampus, Cerebral cortex, Cerebellum, Tectum of midbrain) of these mice were measured by fluorescent probe Ca2+ indicator Fura-2 and an AR-CM-MIC cation measurement system. The results showed that, in comparison with 1-month-old mice, the ability of discrimination learning and memory of 6-month-old ones were attenuated, and the synaptosomal free [Ca2+]i of hippocampus was increased.

Alb, beta 2-m, IgG in serum and urine were determined in 52 burn patients (from January 1993 to December 1994) with RIA technique. The results revealed that there was no obvious connection between the area of burn and the alteration in these parameters (P > 0.05). Our findings indicated a positive correlation between the depth of burn and impairment in the renal function. The recovery of renal function was gradual, and that of glomerulus was earlier than renal tubules. Monitoring of renal function with RIA technique showed a higher sensitivity and accuracy than routine examinations, and it might play an important role in the treatment of burned patients in different periods.

Three pentapeptides have been isolated from the roots of Aster tataricus and their structures elucidated on the basis of spectroscopic analysis as well as chemical and enzymatic methods.

In the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.

Carcinoembryonic antigen (CEA) is frequently used in the diagnosis of the colorectal carcinoma. CA242 is a novel unique tumor-associated antigen characterized by higher tumor specificity and sensitivity for colorectal cancer, as compared with other mucin antigens. In this study, preoperative levels of serum CEA and CA242 were measured in 63 cases of colorectal carcinoma. It was disclosed that the positive rate of CA242 was higher than that of CEA, particularly in patients with colon cancer. The combined determination of CEA and CA242 significantly increased the sensitivity and accuracy in the detection of colorectal cancer as compared with the use of CEA alone (P < 0.01). In patients with advanced disease the positive rate was markedly elevated, especially in patients with liver metastasis. The results indicate that the combined use of CEA and CA242 assays is an useful adjunct diagnostic measure for colorectal carcinoma, and is helpful in the assessment of the stage of the disease as well as in making treatment plan.

Background: An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease., Methods and Results: The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05)., Conclusion: In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.

Two new triterpenoid saponins, aster-yunnanosides F and G, were isolated from the roots of Aster-yunnanensis. Their structures were determined as oleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 3-O-beta-glucopyranosyloleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-[alpha-L-rhamnopyranosyl-(1-->2) ]- beta-D-glucopyranoside by spectral data, especially 2D NMR analysis including COSY, HETCOR, HOHAHA, and ROESY techniques, and chemical transformation.

Purpose: To identify those factors that predict variability in tumor response to 90Y-radioimmunotherapy based on measurement of incorporated activity and physical dimensions of individual tumors and to apply the concept of effective dose to radioimmunotherapy., Methods and Materials: Human colon carcinoma xenografts growing in nude mice were treated with anti-CEA antibodies labeled with 90Y directly or through a bispecific antibody/labeled hapten system. Tumor response was measured as the delay in growth to eight times the treatment volume. Noninvasive activity (based on bremsstrahlung radiation) and dimension measurements were made in these animals at several times after label injection. The following parameters were compared for their ability to predict individual tumor response: (a) injected activity, (b) injected activity times a factor based on average uptake as a function of volume, (c) in vivo activity per volume measured in each animal at a single time, (d) the integral over time of in vivo activity per volume in each animal, and (e) the minimum dose for each animal in a uniformly active ellipsoid whose total activity and dimensions varied over time the same as the tumor., Results and Conclusion: After correcting for differences in injected activity, two parameters account for much of the variability in tumor response. One of these is the general trend of larger tumors to take up less activity per volume. Additional variability can be accounted for by the in vivo activity per volume measurements. The minimum dose as introduced here is likely to be useful in estimating the biologically effective dose delivered by each treatment.

In order to evaluate the accuracy of preoperative segmental localization of hepatic mass lesions, 68 cases were prospectively studied and evaluated by the correlation of magnetic resonance imaging (MRI) and surgical findings. Right, middle and left hepatic veins were seen in 100%, 97% and 94% of the subjects respectively on MRI. The right and left portal veins were seen in 100% and 95.6% respectively. The accuracy in determining the segmental location of hepatic lesions was 89.7%. The accuracy could be increased to 91.3% if the lesion was located at single segment whereas it was only 86.4% when the lesion extended across several segments. It is possible to say that MRI is an important modality in the preoperative segmental localization of masses.