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R E Hurd

Publications and source records attributed to R E Hurd.

At least 37 records · Page 2Linked to original sources
PubMed1991

A procedure for using proton magnetic resonance imaging to determine stereotaxic coordinates of the monkey's brain.

Because of great inter-individual variability in the sizes and configurations of monkey brains, consistent intracerebral stereotaxic placements are not possible when a general brain atlas is relied upon to derive placement coordinates. We describe a procedure that allows the determination of brain atlases for individual monkeys using proton magnetic resonance imaging and the translation of image coordinates to stereotaxic coordinates. The latter is accomplished by chronically implanting glass beads filled with copper sulfate into the skull to establish a plane horizontal to the stereotaxic plane and to provide reference points for zeroing stereotaxic carriers during intracerebral implants. The efficacy of this procedure was confirmed experimentally.

Animals↗
PubMed1990

A double quantum coherence transfer proton NMR spectroscopy technique for monitoring steady-state tumor lactic acid levels in vivo.

If proton nuclear magnetic resonance (1H NMR) spectroscopy is to provide a clinically useful modality for monitoring tumor growth and treatment, the technique must be able to unambiguously detect steady-state metabolite concentrations in human tumors and differentiate these from normal tissue levels. To address this problem, a two-dimensional double quantum coherence transfer spectroscopy (2DDQCT) method was developed and tested in a series of tumor cell lines implanted in mice. Lactate-edited proton NMR spectra were determined from a roughly 1-cm3 region of interest in EMT6, RIF-1, and fibroma. In two-dimensional data matrix representations of the 2DDQCT experiments (double quantum frequency on the vertical axis and chemical shift on the horizontal axis) the lactate signal (330 Hz with the transmitter set at the water resonance) was well-resolved from lipid (480 Hz, 600 Hz). The resolution in the double quantum dimension was also sufficient to conclude that a detectable level of alanine, which would reside at 358 Hz, was not present in the three tumor types. Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively. This technique is likely to provide a noninvasive method for monitoring the steady-state lactic acid levels in small tumors before and after therapy, as well as in tissues with impaired oxygen delivery using clinical and research NMR systems.

Animals↗
PubMed1989

Metabolite specific proton magnetic resonance imaging.

An imaging method is described that makes use of proton double quantum nuclear magnetic resonance (NMR) to construct images based on selected metabolites such as lactic acid. The optimization of the method is illustrated in vitro, followed by in vivo determination of lactic acid distribution in a solid tumor model. Water suppression and editing of lipid signals are such that two-dimensional spectra of lactic acid may be obtained from a radiation-induced fibrosarcoma (RIF-1) tumor in under 1 min and lactic acid images from the same tumor in under 1 hr at 2.0 T. This technique provides a fast and reproducible method at moderate magnetic field strength for mapping biologically relevant metabolites.

Animals↗
PubMed1988

Detection of tumors with 19F magnetic resonance imaging.

Previous 19F magnetic resonance imaging studies showed that the reticuloendothelial system can be imaged with an emulsion of perfluorooctyl bromide (PFOB). Similar techniques can be used to detect previously implanted RIF-1 tumors in mice after intravenous PFOB administration. Accumulation of PFOB within these neoplasms is due to egress of the emulsion through tumor capillary fenestrations. This is the first report in which 19F MRI and PFOB are used to detect tumors. This technique may allow clinical detection of cancer with 19F MRI.

Animals↗
PubMed1984

Thyromimetic effects of 3,5-dimethyl,3'-isopropyl thyronine (DIMIT) and 3,5-diethyl,3'-isopropyl thyronine (DIET) in various tissues of the rat.

We have examined the effects of treatment of the rat with 3,5-dimethyl-3'-isopropyl thyronine (DIMIT) and 3,5-diethyl-3'-isopropyl thyronine (DIET) on serum thyrotropin (TSH) concentration, heart weight, hepatic outer ring (5'-) monodeiodination of T4 to T3, cardiac outer ring monodeiodination of 3'-5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine (3'-T1), and cerebral cortical monodeiodination of 3,5-T2 in the inner ring to 3-T1. Groups of four to seven rats were injected intraperitoneally either once a day or at eight-hour intervals for three days with saline or thyronines. Serum TSH was measured by radioimmunoassay. The various monodeiodinations were studied in homogenates of the tissues at optimal pH (7.35 for outer ring monodeiodinations and 8.0 for inner ring monodeiodination) and temperature (37 degrees C) in the presence of an excess of dithiothreitol. DIMIT was clearly active in all thyromimetic effects studied. It was about 10% as active as T4 in suppression of TSH. It stimulated hepatic monodeiodination of T4 to T3 in a similar manner to T4. DIMIT was also more comparable to T4 than to T3 in effect on heart weight and cardiac metabolism of 3',5'-T2 to 3'-T1. It was highly active, apparently more so than either T4 or T3, in cerebral cortical stimulation of metabolism of 3,5-T2 to 3-T1. In distinction to DIMIT, DIET had very little thyromimetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Inhibition of phagocytosis and chemiluminescence in human leukocytes by a lipid soluble factor in normal tissues.

Homogenates of normal rat tissues inhibited several functional parameters of normal human peripheral blood leukocytes, including luminol-dependent chemiluminescence induced by both soluble (phorbol myristate acetate) and particulate (Escherichia coli) stimuli; in vitro uptake of radiolabeled E. coli; and in vitro phagocytosis and killing of E. coli. The doses of rat tissue protein that caused a 50% inhibition of leukocyte chemiluminescence were ca. 6.2 micrograms for small intestine, 83 micrograms for kidney; 100 micrograms for heart; 132 micrograms for liver, 190 micrograms for skeletal muscle, and 307 micrograms for brain. The putative phagocytosis inhibitor (PI) in rat liver was more plentiful in particulate fractions than in the cytosol. The PI activity in the original or Miranol-solubilized rat liver homogenate was nondialyzable, and it was reduced substantially by heating at 90 degrees C for 30 min but not at 56 degrees C for 30 min. It was unaffected by aprotinin, a potent inhibitor of proteolytic activity. Treatment of tissues with trypsin did not reduce PI activity, whereas treatment with phospholipase A2 clearly increased it. The bulk (up to 88%) of PI in rat liver or small intestine could be extracted by lipid solvents, e.g., diethyl ether. Purified fatty acids were potent inhibitors of leukocyte chemiluminescence; other lipids had little or no inhibiting activity. The various data suggest that (i) normal tissues contain a potent PI and (ii) that the PI is a lipid moiety.

Blood Bactericidal Activity↗
PubMed1984

A radioimmunoassay of 3,5-dimethyl-3'-isopropyl-L-thyronine.

A simple, sensitive, and specific RIA has been developed to measure 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) in unextracted serum. The RIA employs a DIMIT-binding antibody obtained from a rabbit immunized with DIMIT-human serum albumin conjugate and [125I]T3 as the radioligand. 8-Anilino-1-naphthalene sulfonic acid and barbital buffer (0.075 M; pH 8.6) were used to minimize serum binding of DIMIT and [125I]T3. The detection threshold of the RIA was 0.03 microgram/dl. Recovery of nonradioactive DIMIT added to serum averaged 104%. 3,5,3'-Triiodothyroacetic acid cross-reacted maximally (78%) in the RIA, followed by T3 (56%), 3,5-diethyl-3'-isopropyl thyronine (43%), 3,3'-diiodothyronine (T2; 12%), tetraiodothyroacetic acid (6.7%), 3'-monoiodothyronine (T1; 0.54%), 3.5-T2 (0.34%), 3-T1 (0.26%), and T4 (0.25%); rT3, 3',5'-T2, thyronine, iodotyrosines, and KI cross-reacted 0.1% or less. The coefficient of variation averaged 7.4% within an assay and 9.0% between assays. After ip administration of DIMIT to the rat, the mean serum DIMIT concentration rose in a dose-related fashion from less than 0.12 microgram/dl in the controls to 44 micrograms/dl in those receiving 200 micrograms/100 g BW daily for 3 days; serum T4 and TSH levels declined significantly in animals receiving 3.2 micrograms DIMIT/(100 g BW X day) or more. After a single ip injection of DIMIT to the rat, serum DIMIT levels increased from a control value of 0.04 to 9.8 micrograms/dl at 2 h and then decreased progressively, with a half-life approximating 7.2 h. Serum TSH was suppressed for up to 24 h, while serum T4 and T3 were suppressed for up to 48 h after the injection. Concentrations of DIMIT 15 h after a dose of 10 micrograms, ip, to approximately 150-g rats were (nanograms per g; mean +/- SE) 19 +/- 2.3 in serum, 30 +/- 3.5 in liver, 23 +/- 2.4 in kidney, 19 +/- 4.7 in heart, 16 +/- 3.4 in skeletal muscle, and 20 +/- 3.0 in brain. DIMIT administration to pregnant rats [3 micrograms/(100 g BW X day) for 3 days, im] resulted in mean +/- SE DIMIT concentrations (micrograms per dl) of 0.51 +/- 0.14 in maternal serum, 0.57 +/- 0.04 in fetal serum, and 0.46 +/- 0.07 in amniotic fluid. A DIMIT dose of 10 micrograms/(100 g BW X day) for 3 days in maternal rats resulted in mean DIMIT concentrations (micrograms per dl) of 1.8 +/- 0.06 in maternal serum, 1.4 +/- 0.10 in fetal serum, and 1.3 +/- 0.17 in amniotic fluid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Effect of 3,5,3'-triiodothyronine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolic responses.

We studied the effect of T3-induced hyperthyroidism on the outer ring (5' or 3') monodeiodination of T4 (to T3) and 3',5'-diiodothyronine [3',5'-T2; to 3'-monoiodothyronine (3'-T1)] and on the inner ring (3 or 5) monodeiodination of 3,5-T2 (to 3-T1) by various rat tissues. Weight-matched pairs of male Sprague-Dawley rats were given either saline or T3 (20 micrograms/100 g BW daily) ip for 3 days. The metabolism of the iodothyronines was studied on day 4 in homogenates of the tissues in the presence of 25 mM dithiothreitol. Hyperthyroidism was associated with a significant (P less than 0.05) increase in T4 to T3 monodeiodinating activity in the liver (mean, 95%), kidney (mean, 60%), and heart (mean, 153%), but not in skeletal muscle, small intestine, spleen, testis, cerebral cortex, or cerebellum. The monodeiodinating activity converting 3',5'-T2 to 3'-T1 was greatly increased (P less than 0.05) in the heart (mean, 750%), spleen (mean, 462%), and skeletal muscle (mean, 167%), but not in liver, kidney, small intestine, testis, cerebral cortex, or cerebellum. In the case of liver and kidney, however, there was evidence of an activation of 3',5'-T2 monodeiodinating activity, as suggested by a significant increase in the activity in the absence of added dithiothreitol. The monodeiodination of 3,5-T2 to 3-T1 increased significantly only in the cerebral cortex (mean, 525%) and liver (mean, 69%) and not in any other tissue. The time course of the above-mentioned changes in iodothyronine metabolism was studied in groups of rats (five per group) given T3 (20 micrograms 100 g BW-1 day-1) 6-72 h before death. Significant increases in 3',5'-T2 (to 3'-T1) monodeiodination in the heart and 3,5-T2 (to 3-T1) monodeiodination in the cerebral cortex were evident within 6 h of T3 administration. Changes in T4 to T3 monodeiodinating activity in the kidney and liver, however, did not become statistically significant until 24 and 72 h, respectively. The various effects of T3 on the tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

A study of cardiac effects of thyroid hormones: evidence for amelioration of the effects of thyroxine by sodium ipodate.

We studied the effects of daily ip administration of T4 (200 micrograms/100 g BW) or T3 (50 micrograms/100 g) to the rat (six per group) for 3 days with or without sodium ipodate (6 mg/100 g), propylthiouracil (PTU; 2 mg/100 g), propranolol (0.5 mg/100 g), or amiodarone (2.5 mg/100 g) on cardiac weight, 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine monodeiodinating activity (MA), mitochondrial alpha-glycerophosphate dehydrogenase (alpha GPD), and/or cytosolic ornithine decarboxylase (ODC). T4 treatment caused a 28% increase in cardiac weight, about an 11-fold increase in 3',5'-T2 MA, about a 27% increase in alpha GPD activity, and about a 129% increase in ODC activity. Administration of ipodate with T4 abolished all effects of T4 on the heart. PTU abolished the effect of T4 on alpha GPD and markedly reduced its effect on 3',5'-T2 MA and ODC activity; it had little effect on cardiac hypertrophy caused by T4 treatment. Propranolol reduced the increase in cardiac weight following T4 administration from 28% to 11%, but had a modest or no effect on T4-induced changes in other metabolic variables studied. Amiodarone also reduced the effect of T4 on heart weight, but had little or no influence on 3',5'-T2 MA, the only metabolic variable studied. T3 treatment of the rat caused a 35% increase in heart weight, about a 15-fold increase in 3',5'-T2 MA, about a 35% increase in alpha GPD, and about a 100% increase in ODC activity. Ipodate and PTU reduced the increase in 3',5'-T2 MA following T3 administration, but had no appreciable influence on heart weight, alpha GPD, and/or ODC activity. Propranolol and amiodarone had no significant effect on any of the changes studied after T3 administration. It was concluded that: 1) ipodate markedly lessens or abolishes the effects of T4 on the heart; 2) propranolol and amiodarone decrease cardiac hypertrophy in response to T4 administration, but have little or no effect on metabolic changes due to T4; 3) PTU curtails the metabolic effects of T4 on the heart but has little effect on cardiac hypertrophy; 4) none of the drugs studied affects cardiac changes occurring after T3 administration. The changes observed in 3',5'-T2 MA after ipodate and PTU treatment may have been a result of direct interaction of the drugs with the deiodinase.

Amiodarone↗
PubMed1984

A competitive ligand binding assay for measurement of thyroid hormone-binding inhibitor in serum and tissues.

A competitive ligand-binding assay (CLBA) is described for measurement of an inhibitor(s) of serum binding of T4 in ether extracts of serum and in homogenates and extracts of tissues. The CLBA is based on the effect of thyroid hormone binding inhibitor (THBI) on partition of a constant amount of radiolabeled ligand [(125I]T4) between fixed amounts of serum and an anti-T4 antibody. The method is convenient, rapid, sensitive, and reproducible. The coefficient of variation averaged 8.9% within an assay and 12.8% between assays. Several fatty acids, e.g. arachidonic acid, lauric acid, linolenic acid, and linoleic acid, had potent THBI activity in the CLBA; arachidonic acid was more potent than the other fatty acids. Since oleic acid cross-reacted substantially with T4-binding sites on anti-T4, its THBI activity was examined by an equilibrium dialysis method; it was about 77% as potent as arachidonic acid. Arachidic, myristic, palmitic, and stearic acids, choleserol, various phospholipids and triglycerides (triolein and tripalmitin) had little or no THBI activity in the CLBA. THBI activity was detected in the sera of 50% (60% when serum T4 was low and 42% when it was normal) of 34 patients with nonthyroid illnesses (NTI) when studied by CLBA and in 59% (67% when serum T4 was low and 53% when it was normal) of patients when determined by the inhibitory ratio (normalized dialysis ratio/normalized binding ratio). THBI values obtained by the CLBA correlated significantly (r = 0.58; P less than 0.001) with those obtained by the inhibitory ratio method. The dose-response curve of an ether extract of pooled sera of hospitalized patients was parallel to that of arachidonic acid in the CLBA. Among various rat tissues, the small intestine had the most THBI activity in both homogenates and ether extracts of homogenates. Ether (2 vol) extracted about 63% of the THBI activity in small intestine homogenate at pH 5.2. THBI activity was demonstrable in all particulate fractions (especially mitochondria and endoplasmic reticulum) of small intestine homogenate; cytosol contained little or no THBI activity. THBI activity changed little after treatment of small intestine homogenate with trypsin or protease inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1979

Identification of tertiary base pair resonances in the nuclear magnetic resonance spectra of transfer ribonucleic acid.

The low-field hydrogen-bond ring NH proton nuclear magnetic resonance (NMR) spectra of several transfer ribonucleic acids (tRNAs) related to yeast tRNAPhe have been examined in detail. Several resonances are sensitive to magnesium ion and temperature, suggesting that they are derived from tertiary base pairs. These same resonances cannot be attributed to cloverleaf base pairs as shown by experimental assignment and ring current shift calculation of the secondary base pair resonances. The crystal structure of yeast tRNAPhe reveals at least six tertiary base pairs involving ring NH hydrogen bonds, which we conclude are responsible for the extra resonances observed in the low-field NMR spectrum. In several tRNAs with the same tertiary folding potential and dihydrouridine helix sequence as yeast tRNAPhe, the extra resonances from tertiary base pairs are observed at the same position in the spectrum.

Arginine↗
PubMed1979

Nuclear magnetic resonance studies on transfer ribonucleic acid: assignment of AU tertiary resonances.

The hydrogen-bonded ring NH nuclear magnetic resonance (NMR) spectra of several transfer ribonucleic acid (RNA) species have been examined with particular emphasis on the extreme low-field portion. Betwen --13.8 and --15 ppm there are two extra resonances which are not derived from cloverleaf base pairs. A combined approach involving undermodified tRNAs, chemical modification, and hairpin fragment studies has assigned the T54--A58 resonance at --14.3 ppm in yeast tRNAPhe and Escherichia coli tRNA1 Val., the U8--A14 resonance has been assigned at --14.3 ppm, and the s4U8--A14 resonance in bacterial tRNAs has been assigned at --14.9 ppm. The T54--A58 resonance shifts between --14.3. and --13.8 ppm depending on the surrounding nucleotide sequence in the ribothymidine loop.

Base Composition↗
PubMed1979

Paramagnetic ion effects on the nuclear magnetic resonance spectrum of transfer ribonucleic acid: assignment of the 15--48 tertiary resonance.

We have studied the effects of Co2+ and Mn2+ ions on the low-field nuclear magnetic resonance (NMR) spectra of pure class 1 transfer ribonucleic acid (tRNA) species. With 1.2 mM tRNA in the presence of 15 mM MgCl2 discrete paramagnetic effects were observed for Co2+ at concentrations in the range 0.02--0.1 mM and for Mn2+ in the range 0.002--0.01 mM, indicating fast exchange of these cations with tRNA. Both of these cations paramagnetically relax the s4U8--A14 resonance as well as other resonances from proximal base pairs. The Co2+ site appears to be the same site on G15 which was observed crystallographically [Jack, A., Ladner, J. E., Rhodes, D., Brown, R. S., & Klug, A. (1977) J. Mol. Biol. 111, 315-328]; the initially occupied tight Mn2+ site is the cation site involving the phosphate of U8. There are three base pairs within 10 A of both sites, namely, G15--C48, A14--s4U8, and C13--G22; this has led to the assignment of the G15--C48 and C13--G22 resonances in the NMR spectrum [Jack, A., Ladner, J. E., Rhodes, D., Brown, R. S., & Klug, A. (1977) J. Mol. Biol. 111, 315--328; Holbrook, S. R., Sussman, J. L., Warrant, R. W., Church, G. M., & Kim, Sung-Hou (1977) Nucleic Acids Res. 4, 2811--2820; Quigley, G. J., Teeter, M. M., & Rich, A. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 64--68].

Cobalt↗
PubMed1979

Nuclear magnetic resonance studies on the tertiary folding of transfer ribonucleic acid: assignment of the 7-methylguanosine resonance.

Analysis of the low-field nuclear magnetic resonance (NMR) spectra of several class 1 D4V5 transfer ribonucleic acid (tRNA) species containing 7-methylguanosine in their variable loops reveals a set of six to seven tertiary base pair resonances, one of which is always located at ca. --13.4 ppm. Other tRNA species which do not contain 7-methyl-guanosine do not contain the tertiary resonance at --13.4 ppm. Chemical removal of 7-methylguanosine from several tRNAs containing the same dihydrouridine (DHU) helix sequence as yeast tRNAPhe results in the loss of the --13.4-ppm tertiary resonance. In the initiator methionine tRNA, which contains a different DHU helix sequence, the 7-methylguanosine hydrogen bond has been assigned at --14.55 ppm by chemical removal of this residue. In these experiments the aromatic C8H proton of 7-methylguanosine was also assigned (--9.1 ppm). The unexpectedly low-field position of the 7-methylguanosine resonance is explained by the deshielding effect of the delocalized positive charge in this nucleoside.

Base Composition↗
PubMed1977

High-resolution nuclear magnetic resonance determination of transfer RNA tertiary base pairs in solution. 1. Species containing a small variable loop.

Eight class I tRNA species have been purified to homogeneity and their proton nuclear magnetic resonance (NMR) spectra in the low-field region (-11 to -15 ppm) have been studied at 360 MHz. The low-field spectra contain only one low-field resonance from each base pair (the ring NH hydrogen bond) and hence directly monitor the number of long-lived secondary and tertiary base pairs in solution. The tRNA species were chosen on the basis of their sequence homology with yeast phenylalanine tRNA in the regions which form tertiary base pairs in the crystal structure of this tRNA. All of the spectra show 26 or 27 low-field resonances approximately 7 of which are derived from tertiary base pairs. These results are contrary to previous claims that the NMR spectra indicate the presence of resonances from secondary base pairs only, as well as more recent claims of only 1-3 tertiary resonances, but are in good agreement with the number of tertiary base pairs expected in solution based on the crystal structure. The tertiary base pair resonances are stable up to at least 46 degrees C. Removal of magnesium ions causes structural changes in the tRNA but does not result in the loss of any secondary or tertiary base pairs.

Binding Sites↗
PubMed1977

High-resolution nuclear magnetic resonance determination of transfer RNA tertiary base pairs in solution. 2. Species containing a large variable loop.

The number of base pairs in the solution structure of several class III D3VN tRNA species from E. coli has been determined by analyzing the number of low-field (-15 to -11 ppm) proton resonances in their nuclear magnetic resonance spectra at 360 MHz. Contrary to previous reports indicating the absence of tertiary resonances, all the spectra exhibit the expected number of secondary base pair resonances plus approximately ten extra resonances derived from tertiary base pairs in the three-dimensional folding of these molecules. The possible origins of some of these tertiary resonances are discussed; none of the spectra exhibits the characteristic resonance of the 8-14 tertiary base pair seen in class I D4V5 tRNA spectra.

Binding Sites↗