Artifacts from pulsatile flow in MR imaging.

Previous investigators have examined the effect of blood flow on the apparent blood vessel signal intensity. These studies reported flow brightening and darkening effects within vessels. In this paper we have investigated another type of flow artifact, which originates from the pulsatile nature of blood flow.

Preparation of (6R)-tetrahydrofolic acid and (6R)-5-formyltetrahydrofolic acid of high stereochemical purity.

Commercially available 5-formyltetrahydrofolate (5-CHO-H4PteGlu) is chemically prepared in a reaction that introduces an asymmetric center at the 6 carbon, and hence is the mixture of diastereomers differing in chirality about this position. (6R)-5-CHO-H4PteGlu, the diastereomer that is not normally found in vivo, was prepared from folic acid. Folic acid was chemically reduced and (6R)-tetrahydrofolate (H4PteGlu) was obtained from the resultant (6R,S)-H4PteGlu by enzymatic consumption of the natural diastereomer of (6R,S)-5,10-CH2-H4PteGlu (reversibly formed from (6R,S)-H4PteGlu in the presence of formaldehyde) with Lactobacillus casei thymidylate synthase.

Methotrexate analogues. 26. Inhibition of dihydrofolate reductase and folylpolyglutamate synthetase activity and in vitro tumor cell growth by methotrexate and aminopterin analogues containing a basic amino acid side chain.

Analogues of the antitumor antifolate methotrexate (MTX) were synthesized in which the glutamate (Glu) moiety was replaced by ornithine (Orn), 2,4-diaminobutyric acid (Dab), or 2,3-diaminopropionic acid (Dap). An aminopterin (AMT) analogue with Orn in place of Glu was also synthesized. The MTX analogues were obtained by reaction of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) and N omega-Boc-alpha,omega-diaminoalkanoic acids in the presence of diethyl phosphorocyanidate, followed by deprotection with trifluoroacetic acid (TFA) or by reaction of p-nitrophenyl-mAPA and N omega-Boc-alpha,omega-diaminoalkanoic acids and subsequent treatment with TFA.

Childhood Menetrier's disease: four new cases and discussion of the literature.

Four cases of childhood Menetrier's disease are presented and their clinical and laboratory findings are compared with the other childhood cases reported in the literature. Children with Menetrier's disease usually present with abdominal pain or nausea and vomiting associated with peripheral edema, ascites, or pleural effusion; these symptoms are due to gastrointestinal protein loss and resultant hypoproteinemia. There is no evidence of urinary protein loss.

The drooling patient: team evaluation and management.

Drooling is a common problem in neurologically damaged individuals. A surgeon, speech pathologist, physiotherapist and dentist created a "team" to evaluate affected patients. Management by consensus involves both non-surgical and surgical modalities.

Detection of 5-bromodeoxyuridine (BrdUrd) incorporation by monoclonal antibodies: role of the DNA denaturation step.

Immunochemical detection of cells that incorporate 5-bromodeoxyuridine (BrdUrd) requires prior denaturation of DNA in situ to make BrdUrd binding sites accessible to the antibodies. A technique is described in which the DNA denaturation step is facilitated by a) prior dissociation of histones from DNA and b) the use of low ionic strength buffer in which the cells are suspended during heating. Dissociation of histones is achieved by cell treatment with 0.

Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin.

Total syntheses from pyridine precursors of 5,10-dideazaaminopterin (1) and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin (2) are described. These compounds exhibit significant in vivo activity against L1210 leukemia that is comparable to that observed with methotrexate.

Simultaneous MR imaging of both breasts using a dedicated receiver coil.

We have designed and built a dedicated magnetic resonance (MR) coil that images both breasts simultaneously with the patient in a prone position, incorporates imaging advantages of surface coils, and benefits from having separate transmitter and receiver coils. This coil is compatible with a 0.15-T (6.

Verification and evaluation of internal flow and motion. True magnetic resonance imaging by the phase gradient modulation method.

We report qualitative and quantitative evaluation and verification studies of the bipolar phase gradient modulation method for true MR imaging of internal flow and motion velocities. Velocity encoding modulations provide speed-of-motion and direction-sensitive images using special phase-sensitive reconstructions. True motion MR imaging does not depend upon subject parameters, T1 or T2, nor upon selective active-volume time-of-flight calculations, nor is it limited strictly to fluid-flow velocities.

Structural features of 4-amino antifolates required for substrate activity with mammalian folylpolyglutamate synthetase.

The activity of a series of folic acid analogues as substrates for partially purified mouse liver folylpolyglutamate synthetase was determined and the effects of substituents on the binding to, and catalytic processes of, this enzyme were inferred. A 4-amino group improved substrate activity primarily by decreasing the apparent Km while N10-methyl substitution substantially diminished utilization as a substrate, again, by effects on Km. Isosteric replacement of N-10 altered substrate activity.

Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer.

DNA ploidy and percent of (%S-phase) S-phase cells were determined from the DNA content distribution of 21 benign and 76 malignant (69 primary, 7 metastatic) breast tumors using flow cytometry. All of the benign tumors were diploid, whereas 89% of the malignant tumors had measurable aneuploidy. Multiple stem-lines were observed in approximately 10% of the malignant tumors.

A mechanism for the addition of multiple moles of glutamate by folylpolyglutamate synthetase.

The role of the alpha-carboxyl group in methotrexate (MeAPA-Glu) and the gamma-glutamate derivative of methotrexate (MeAPA-Glu-Glu) in the reaction catalyzed by folylpolyglutamate synthetase (FPGS) has been investigated. MeAPA-Glu and MeAPA-Glu-Glu were accepted as substrates by the same FPGS species contained in an (NH4)2SO4 precipitate of mouse liver protein, as judged by a lack of additivity of product formation at saturating concentrations of both substrates. MeAPA-Gaba, the MeAPA-Glu analogue lacking an alpha-carboxyl, was inactive as a substrate for this enzyme as was MeAPA-Glu-Gaba, the analogue of MeAPA-Glu-Glu that lacked the alpha-carboxyl of the terminal glutamic acid.

Mammalian folyl polyglutamate synthetase: partial purification and properties of the mouse liver enzyme.

Folyl polyglutamate synthetase has been partially purified from mouse liver, and the general features of this enzyme have been characterized. The purification procedure utilized fractionation with ammonium sulfate, gel filtration, and affinity chromatography on ATP-agarose and resulted in a 350-fold increase in specific activity with 8-20% recovery of enzyme activity. Enzyme could be stabilized by glycerol or by ATP, but stability was not appreciably enhanced by folate.

Measurement of folylpolyglutamate synthetase in mammalian tissues.

Previous methods for the measurement of folylpolyglutamate synthetase have been modified and combined to facilitate assay of this enzyme at the levels found in mammalian tissues. Batch adsorption of product onto charcoal allowed the rapid analysis of multiple samples of partially purified enzyme, e.g.

Flow cytometric analysis of human lung cancer. Correlation with histologic type and stage.

DNA ploidy and cell-cycle characteristics of 65 operable lung cancers (41 adenocarcinomas, 19 epidermoid carcinomas, 3 large-cell carcinomas and 2 small-cell carcinomas) were analyzed using flow cytometry. Eighty percent of the tumors were aneuploid. The mean DNA index was lower in epidermoid than in adenocarcinoma.

Methotrexate analogues. 19. Replacement of the glutamate side chain in classical antifolates by L-homocysteic acid and L-cysteic acid: effect on enzyme inhibition and antitumor activity.

Methotrexate (MTX) and aminopterin (AMT) analogues containing L-homocysteic acid or L-cysteic acid in place of L-glutamic acid were synthesized and tested as inhibitors of dihydrofolate reductase from L1210 cells and folyl polyglutamate synthetase from mouse liver. The ID50 against dihydrofolate reductase was comparable for the MTX and AMT analogues (0.04-0.

A rapid and convenient preparation of [4-3H]NADP and stereospecifically tritiated NADP3H.

The enzymatic preparation and chromatographic purification of [4-3H]NADP and NADPH stereospecifically labeled with 3H on either the A or B faces at position 4 have been simplified. Commercially available [1-3H]glucose was used as a starting material for the sequential synthesis of [4B-3H]NADPH, [4-3H]NADP, and [4A-3H]NADPH. These products were rapidly purified by step elution of DEAE-cellulose minicolumns so that [4B-3H]NADPH was produced and purified from [1-3H]glucose in 2 h, [4-3H]NADP in 5 h, and [4A-3H]NADPH in 8 h.

Methotrexate analogues--XVII. Antitumor activity of 4-amino-4-deoxy-N10-methylpteroyl-D,L-homocysteic acid and its dual inhibition of dihydrofolate reductase and folyl polyglutamate synthetase.

A new analogue of methotrexate was synthesized from 4-amino-4-deoxy-N10-methylpteroic acid and D,L-homocysteic acid. The product (mAPA-HCysA) was bound tightly to L1210 mouse leukemia dihydrofolate reductase (IC50 = 1 nM), inhibited L1210 cell proliferation in culture (IC50 = 0.3 microM), and prolonged the survival of L1210 leukemic mice (98% increase in lifespan at 120 mg/kg, qdx9).

Labeling indices of human lung cancer. Correlation with histologic type and survival.

The labeling index (LI) of tumor specimens from 28 patients (9 primary, 21 metastases) with lung cancer was analyzed after in vivo 3H-thymidine labeling. The mean LI was 11.1 (range, 1.

Localization of globoside and Forssman glycolipids on erythrocyte membranes.

Using the freeze-etch technique, the membrane localization of globoside, a principal glycolipid in human erythrocytes, and Forssman antigen, the chief glycolipid in sheep erythrocytes was evaluated using ferritin and colloidal gold as morphological markers for rabbit antibodies prepared against these glycolipids. Brief trypsinization of human red cell ghosts markedly aggregated intramembranous particles and permitted labeling of globoside, which appeared in a clustered arrangement. The aggregates of ferritin-anti-globoside differed from those of ferritin-wheat germ agglutinin, a label for glycophorin, which corresponded with the aggregates of intramembranous particles.

Angiotensin-converting enzyme inhibitory activity of SCH 31846, a new non-sulfhydryl inhibitor.

SCH 31846, 1-(N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanyl)-cis, syn-octahydro-(H-indole-2-S)-carboxylic acid; CI-907; PD 109, 763-2, is a new non-sulfhydryl-containing, angiotensin-converting enzyme (ACE) inhibitor. The present investigation describes its ACE inhibitory properties and compares them to those of MK 421. The diacid of SCH 31846 inhibited rabbit pulmonary ACE with an IC50 of 2.