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Biomedical subjects

R E Hurd

Publications and source records attributed to R E Hurd.

At least 19 recordsLinked to original sources
PubMed2004

In vivo 2D J-resolved magnetic resonance spectroscopy of rat brain with a 3-T clinical human scanner.

A clinical 3-T scanner equipped with a custom-made transmit/receive birdcage coil was used to collect 2D J-resolved single-voxel spectroscopy in vivo of rat brain. Four adult Wistar rats were scanned twice each, with a 2-week interval. Voxel size was approximately 5 x 10 x 5 mm(3). Total spectroscopic acquisition time was 14 min for collection of two 4:20 min water-suppressed acquisitions and one 4:20 min acquisition acquired in the absence of water suppression. The unsuppressed water data were used in post-processing to reduce residual water side bands, as well as for metabolite signal normalization to account for variations in coil loading and voxel size. Peak areas were estimated for resonances from N-acetyl aspartate (NAA), creatine, choline, taurine, glutamate, and combined glutamate and glutamine. T(2)-relaxation times were estimated for NAA and creatine. The average deviation from the mean of repeated measures for glutamate, combined glutamate and glutamine, and taurine ranged from 7.6% to 18.3%, while for NAA, creatine, and choline, the deviation was less than 3%. The estimated T(2) values for NAA (mean +/- SD = 330 +/- 57 ms) and creatine (174 +/- 27 ms) were similar to those reported previously for rat brain and for human gray and white matter. These results indicate that reliable, small animal brain MR spectroscopy can be performed on a human clinical 3-T scanner.

Anesthesia↗
PubMed2002

Retinal degeneration mutants in the mouse.

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to look for genetically determined eye variations and disorders. Through ophthalmoscopy, electroretinography and histology, we have discovered disorders affecting all aspects of the eye including the lid, cornea, iris, lens and retina, resulting in corneal disorders, cataracts, glaucoma and retinal degenerations. Mouse models of retinal degeneration have been investigated for many years in the hope of understanding the causes of photoreceptor cell death. Sixteen naturally occurring mouse mutants that manifest degeneration of photoreceptors in the retina with preservation of all other retinal cell types have been found: retinal degeneration (formerly rd, identical with rodless retina, r, now Pde6b(rd1)); Purkinje cell degeneration (pcd); nervous (nr); retinal degeneration slow (rds, now Prph(Rd2)); retinal degeneration 3 (rd3); motor neuron degeneration (mnd); retinal degeneration 4 (Rd4); retinal degeneration 5 (rd5, now tub); vitiligo (vit, now Mitf(mi-vit)); retinal degeneration 6 (rd6); retinal degeneration 7 (rd7, now Nr2e3(rd7)); neuronal ceroid lipofuscinosis (nclf); retinal degeneration 8 (rd8); retinal degeneration 9 (Rd9); retinal degeneration 10 (rd10, now Pde6b(rd10)); and cone photoreceptor function loss (cpfl1). In this report, we first review the genotypes and phenotypes of these mutants and second, list the mouse strains that carry each mutation. We will also provide detailed information about the cpfl1 mutation. The phenotypic characteristics of cpfl1 mice are similar to those observed in patients with complete achromatopsia (ACHM2, OMIM 216900) and the cpfl1 mutation is the first naturally-arising mutation in mice to cause cone-specific photoreceptor function loss. cpfl1 mice may provide a model for congenital achromatopsia in humans.

Animals↗
PubMed2001

Single-voxel oversampled J-resolved spectroscopy of in vivo human prostate tissue.

Single-voxel J-resolved spectroscopy with oversampling in the F1 dimension was used to obtain water unsuppressed 1H spectra of in situ human prostate tissue in 40 previously untreated prostate cancer patients. Based on T2-weighted MRI and previous biopsy information, voxels were placed in regions of benign or malignant peripheral zone tissue, or in regions of predominantly glandular or stromal benign prostatic hyperplasia (BPH) within the central gland. The addition of a second J-resolved dimension allowed for the observation of the J-modulation of citrate, as well as the resolution of polyamines from overlapping choline and creatine signals. Regions of healthy peripheral zone tissue and glandular BPH all demonstrated high levels of citrate and polyamines, with consistent coupling and J-modulation patterns. Conversely, regions of malignant peripheral zone tissue and stromal BPH demonstrated low levels of citrate and polyamines consistent with prior in vivo and ex vivo studies. Moreover, water T2 relaxation times determined for healthy peripheral zone tissue (mean 128 +/- 15.2 msec) were significantly different than for malignant peripheral zone tissue (mean 88.0 +/- 14.2 msec, P = 0.005), as well as for predominantly glandular (mean 92.4 +/- 12.2 msec, P = 0.009) and stromal BPH (mean 70.9 +/- 12.1 msec, P = 0.003). This preliminary study demonstrates that J-resolved spectroscopy of the in situ prostate can be acquired, and the information obtained from the second spectral dimension can provide additional physiologic information from human prostate tissue in a reasonable amount of time (< 10 min).

Aged↗
PubMed1998

Proton spectroscopy without water suppression: the oversampled J-resolved experiment.

A method is introduced for obtaining proton spectra in vivo with all the advantages of a full water signal. The method, based on F1 oversampled J-resolved spectroscopy, makes it possible to separate metabolite signals from unwanted baseline artifacts. The dominant water resonance is used as a 2D reference signal for the phase-sensitive reconstruction of the 2D J-resolved metabolite spectra. The powerful specificity of this method is demonstrated with model compound spectra, phantoms, and in vivo examples.

Adult↗
PubMed1997

Imaging of shifted stimulated echoes and multiple spin echoes.

It is shown that a repetitive pulse sequence consisting of two 90 degrees pulses and gradients in a 1:2 ratio around the second 90 degrees pulse generates interscan shifted stimulated echoes (SSTEs) and intrascan multiple spin echoes (MSEs). Separation of these two types of signals is accomplished using specific gradient crusher schemes. The intensity of the SSTEs is an order of magnitude larger than that of the MSEs and determines the signal contrast if both effects are selected simultaneously. The SSTE sequence generates improved contrast between gray and white matter, even at high field, which is explained in terms of increased inverse T1-weighting for the interscan echo. The MSE image has low signal to noise and no detectable contrast. The effect of interscan diffusion weighting is also discussed.

Animals↗
PubMed1996

Quantitation of automated single-voxel proton MRS using cerebral water as an internal reference.

Data from a previously published, multi-site trial (P.G. Webb, N. Sailasuta, S.J. Kohler, T. Raidy, R.A. Moats, R.E. Hurd. Automated single-voxel proton MRS: technical development and multisite verification. Magn. Reson. Med. 31, 365-373 (1994)) of a fully automatic, single-voxel, proton spectroscopy package (PROBE/SV, GE Medical Systems) was re-analyzed in terms of absolute metabolite concentrations using the cerebral water signal as an internal reference. In 100 spectra from parietal white matter in normal volunteers ranging in age from 22 to 34 years at eight sites, overall concentrations of choline (Cho) creatine (Cr), and N-acetyl-aspartate (NAA) resonances were found to be 2.00 +/- 0.50, 8.43 +/- 1.28, and 12.55 +/- 1.76 mumol/g wet weight, respectively. These values are in good general agreement with previously published values from quantitative, single-voxel studies. Metabolite concentrations for NAA, Cr, and Cho across all sites had standard deviations of 14.1%, 14.9%, and 25.1%, respectively. Quantitation of PROBE data sets is routinely possible by using the cerebral water signal as an internal reference.

Cerebral Cortex↗
PubMed1994

Automated single-voxel proton MRS: technical development and multisite verification.

To improve clinical utility, an integrated method has been developed to automatically acquire and process single-voxel in vivo proton spectra on a 1.5 T clinical scanner. This method includes automated adjustment of linear shims using a very rapid modified simplex method, automated water suppression, and applies a water referencing scheme to correct for phase and residual eddy current effects. No operator intervention is required for the acquisition and processing of these pure-absorption spectra. This method was tested in a preliminary multisite trial to determine intersite and intrasite variability of metabolite ratio measurements. In a sample of over 100 examinations, the standard deviation of the ratios NAA:Cr, Cho:Cr, and ml:Cr were found to be under 15% when using this method, a substantially narrower range than has been found in studies relying on manual adjustment of the instrument and/or manual processing. This result indicates that automated setting of acquisition and processing parameters is of critical importance in the clinical application of in vivo spectroscopy.

Algorithms↗
PubMed1994

Sex-related differences in iodothyronine metabolism in the rat: evidence for differential regulation among various tissues.

Various aspects of thyroid hormone metabolism were examined in vitro in age-matched (experiment I) and weight-matched (experiment II) male and female Sprague-Dawley rats; unless specified otherwise, results were similar in both experiments. The activity and content of iodothyronine 5'-monodeiodinase (type I-MD) in the liver of the female rat were markedly reduced, but there was no sex-related difference in these parameters in the kidney. The activity of the brain type III-MD was also not significantly influenced by the sex of the rat. Hepatic triiodothyronine (T3) sulfation activity in the females was only about 20% of that of the males. However, kidney and brain did not show this decrease in T3 sulfation. Similarly, hepatic T3 sulfate (T3S) desulfation activity was significantly reduced in the liver of the female rat (P < .001), whereas the activity in the kidney was either similar to (experiment I) or higher than (experiment II) that in the male, and the activity in the brain was similar in the two sexes. The mean serum T3S concentration in the female rat was no greater than 25% of the corresponding value measured in the male rat. The mean serum thyroxine (T4) concentration in female rats was similar to that in age-matched males (experiment I), whereas it was somewhat lower than that in weight-matched males (P < .05, experiment II). No significant difference in the mean serum T3 concentration was observed in rats of female and male sex. However, the mean serum thyrotropin (TSH) concentration in the female rat was significantly lower than that in the male.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Thyromimetic effects of 3,5,3'-triiodothyronine sulfate in hypothyroid rats.

Several parameters of the effects of thyroid hormone were examined in hypothyroid thyroidectomized (Tx) rats treated with T3 sulfate (T3S) or T3 [0.46 (low dose) or 2.3 (high dose) nmol/day for 10 days, ip]. Tx rats showed a marked degree of growth retardation, which improved significantly after treatment with both doses of T3S and T3. The mean serum GH level was markedly reduced in Tx rats, and it improved significantly to similar levels after treatment with the high dose of T3S and the low dose of T3. Type I monodeiodinase (MD) activity was markedly reduced in liver and kidney tissues of Tx rats. It increased significantly in Tx rats treated with the high dose of T3S; the latter values were similar to those observed in Tx rats treated with the low dose of T3. Hepatic and renal type I MD activities increased to supranormal levels in Tx rats treated with the high dose of T3. Cardiac outer ring (5') monodeiodination of 3',5'-diiodothyronine to 3'-monoiodothyronine was also significantly reduced in Tx rats, but it improved significantly only after treatment with the high dose of T3. Type III 5-MD activity was significantly reduced in the cerebral cortex of Tx rats. It was restored to normal in Tx rats treated with the high dose of T3S and both doses of T3. Serum TSH, markedly elevated in Tx rats, was appreciably reduced only in rats treated with the high dose of T3. In another study, significant suppression of serum TSH was observed when Tx rats were treated with T3S (11.5 nmol/day) or T3 (2.3 nmol/day) for 3 days. We conclude that administration of T3S to hypothyroid rats produces thyromimetic effects, with a potency approximately one fifth that of T3.

Animals↗
PubMed1993

A study of the 3,5,3'-triiodothyronine sulfation activity in the adult and the fetal rat.

We have employed a new in vitro assay for study of the T3 sulfation activity in rat tissues. The assay measures by RIA the generation of T3 sulfate (T3S) during incubation of T3 with cytosol of rat tissues as the source of phenol sulfotransferase(s) and 3-phosphoadenosine-5'-phosphosulfate as the sulfate donor. The conversion of T3 to T3S proceeded rapidly for 30 min at 37 C, and the optimal pH of the reaction was 8.0. Heating the cytosol at 44 C for 15 min decreased T3S production to 63% of its value at 37 C. T3 sulfation activity was plentiful in rat liver, brain, and kidney, but little activity was demonstrable in other tissues. The Km and maximum velocity of the hepatic conversion of T3 to T3S were 114 microM and 159 pmol/mg protein.h, respectively. There was a marked inhibition of the conversion of T3 to T3S with salicylamide, 3'-monoiodothyronine, thyronine, and rT3; the IC50 of these inhibitors approximated 15, less than 0.1, 9.5, and 43 microM, respectively. On day 17 of gestation, the T3 to T3S conversion activity was more abundant in fetal skin than in other fetal tissues. However, the activity decreased in fetal skin while it increased in fetal liver, kidney, and brain nearer to term on day 20. Placenta demonstrated lower T3 to T3S conversion activity than several fetal or maternal tissues. There was no effect of hypothyroidism or hyperthyroidism on T3 sulfation activity. We conclude that T3 sulfation activity in the rat is 1) most abundant in liver, kidney, and brain tissues of the adult; 2) inhibited more avidly by 3'-monoiodothyronine than other thyronines; 3) very abundant in fetal skin early in gestation; and 4) little affected by the thyroidal status of the animal.

Animals↗
PubMed1993

A radioimmunoassay for measurement of thyroxine sulfate.

A highly sensitive, specific, and reproducible RIA has been developed to measure T4 sulfate (T4S) in ethanol extracts of serum. rT3 sulfate (rT3S) cross-reacted 7.1%, and T3S cross-reacted 0.59% in the RIA; T4, T3, rT3, and 3,3'-diiodothyronine cross-reacted 0.004% or less. The recovery of nonradioactive T4S added to serum averaged 95%. The detection threshold of the RIA was 18 pmol/L. The coefficient of variation averaged 6.9% within an assay and 12% between assays. T4S was bound by T4-binding globulin and albumin in serum. The free fraction of T4S in four normal sera averaged 0.06% compared to a value of 0.03% for T4 (P < 0.001). The serum concentration of T4S was (mean +/- SE) 19 +/- 1.2 pmol/L in normal subjects, 33 +/- 10 in hyperthyroid patients with Graves' disease, 42 +/- 15 in hypothyroid patients, 34 +/- 6.9 in patients with systemic nonthyroidal illnesses, 21 +/- 4.3 in pregnant women at 15-40 weeks gestation, and 245 +/- 26 in cord blood sera of newborns; the value in the newborn was significantly different from normal (P < 0.001). The mean concentration of T4S in amniotic fluid samples at 15-38 weeks gestation was 106 +/- 22 pmol/L (cf. normal adults; P < 0.001). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hyperthyroid patients was associated with a transient increase in serum T4S. The T4S content of the thyroid gland was less than 1/4000th that of T4. We conclude that 1) T4S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid; and 2) the sulfation pathway plays an important role in the metabolism of T4 in man.

Blood Proteins↗
PubMed1992

A study of the characteristics of the rat placental iodothyronine 5-monodeiodinase: evidence that it is distinct from the rat hepatic iodothyronine 5'-monodeiodinase.

Recent studies have demonstrated that rat liver type I iodothyronine 5'-monodeiodinase (5'-MD) characteristically contains selenocysteine. The present study was undertaken to characterize rat placental type III iodothyronine 5-MD and to compare it with 5'-MD. Solubilized rat placental microsomes were delipidated by carboxymethyl cellulose-Sephadex chromatography. Phospholipids and proteins were recovered in two distinct peaks, which did not show 5-MD activity. 5-MD activity was recovered fully, however, by combining the two components (phospholipids and protein) and partially after the addition of exogenous phospholipids to protein. Tissue selenoproteins were labeled by injection of radioactive selenium (75Se; 50 microCi, iv; on days 5, 10, and 15 of gestation) to pregnant rats. Subcellular fractions of maternal and fetal tissues were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. No specific seleno-labeled proteins were evident in the microsomes of placenta or maternal or fetal brain. A 27- to 29-kilodalton (kDa) band previously suggested to be 5'-MD was observed, however, in maternal liver and kidney microsomes. Aurothioglucose inhibited rat placental 5-MD, but the dose required for 50% inhibition was over 50-fold greater than that for Se-containing hepatic 5'-MD (430 vs. 8 nM). The mechanism of the inhibition was noncompetitive for 5-MD, whereas it was competitive for 5'-MD. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blots studies using the rabbit antiserum showed one specific 29-kDa band in rat liver microsomes. However, no specific bands were observed in 5-MD-rich placental or fetal brain microsomes. Bromoacetyl T3 (BrAcT3) was a potent inhibitor of rat placental 5-MD. Affinity labeling of solubilized rat placental microsomes with [125I]BrAcT3 showed a predominant band of 31 kDa, distinct from the 27- to 29-kDa band found in liver and kidney. The labeling of the 31-kDa band was enhanced by 10 mM dithiothreitol, inhibited 60% by 150 microM T3, and prevented by 40 microM aurothioglucose. A dominant affinity-labeled 31-kDa band was also observed in fetal brain microsomes. Some tissues without 5-MD activity (testes and spleen) also showed weak binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A study of the characteristics of hepatic iodothyronine 5'-monodeiodinase in various vertebrate species.

Rat type I iodothyronine 5'-monodeiodinase (5'-MD) has recently been shown to be a selenium-containing enzyme. In the present study we compared the characteristics of the 5'-MD from liver microsomes of rat, mouse, guinea pig, man, beef, pig, sheep, and chicken. Aurothioglucose (ATG), a known potent inhibitor of selenium-containing enzymes, was a consistent, very potent inhibitor of 5'-MD activity in all species studied, with a 50% inhibitory dose in the narrow range of 5.8-12 nM. ATG was also a potent and selective inhibitor of [125I]bromoacetyl T3 affinity labeling of 5'-MD. Thus, in the species studied, only one affinity-labeled band, which was selectively displaced by gold, was identified. The mol wt of the affinity-labeled proteins in various liver microsomal preparations ranged between 28-36 kilodaltons (kDa), and the ATG concentrations necessary for the inhibition of affinity labeling of microsomes with [125I]bromoacetyl T3 were comparable to those required for inhibition of the enzyme activity in all species except the pig. The pig liver microsomes demonstrated a dominant affinity-labeled 36-kDa band, but much higher ATG concentrations (micromolar) were required for inhibition of affinity labeling. In view of the potent inhibition of pig liver 5'-MD activity by ATG, it appears unlikely that this band in the pig corresponds only to the substrate-binding site of 5'-MD, but this issue requires further study. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of rat 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blot studies using the rabbit antiserum showed one specific 29-kDa band in rat liver and kidney microsomes and thyroid homogenate. No specific bands were observed in other adult rat tissues studied or in fetal rat liver. No specific bands were observed when Western blot studies with antibody against the carboxy-terminal portion of rat 5'-MD were performed in liver microsomes from species other than the rat. In conclusion, our studies indicate that selenium is a likely component of type I 5'-MD in all species studied. However, substantial structural differences exist between the rat type I 5'-MD and that in various other species.

Affinity Labels↗
PubMed1992

A study of metabolism of deaminated and sulfoconjugated iodothyronines by rat placental iodothyronine 5-monodeiodinase.

The interaction of the rat placental type III iodothyronine 5-monodeiodinase (5-MD) with acetic acid (AA), propionic acid (PA), and sulfoconjugate (SA) derivatives of thyroid hormones has been investigated in comparison with hepatic iodothyronine type I MD. PA and AA derivatives of both T3 and T4 were potent inhibitors of 5-monodeiodination of [125I]T3 by rat placental microsomes. 3,5,3'-Triiodothyroacetic acid (T3AA) and 3,5,3'-triiodothyropropionic acid (T3PA) were comparable to T3 in their ability to inhibit 5-monodeiodination of [125I]T3, whereas T4AA and T4PA were more potent than T4. 3,5,3'-triiodothyrosulfonic acid (T3SA), T4SA, and rT3SA caused little or no inhibition of placental 5-MD activity. Among various analogs of T3 or T4, the order of relative potency of inhibition of hepatic 5'-MD was PA > AA > SA > parent iodothyronine. The metabolism of T3 and its derivatives by rat placental microsomes was studied by determining the rates of disappearance of the various substrates and the production of the metabolites generated by inner ring monodeiodination of the substrate. T3AA and T3PA were metabolized at a rate comparable to that of T3. Under the same conditions, essentially 100% of T3SA remained intact. Kinetic studies of placental inner ring monodeiodination of T3, T3AA, and T3PA demonstrated comparable values for Km (1.3, 1.8, and 2.3 nM, respectively) and maximum velocity (44, 57, and 74 fmol/micrograms.h, respectively). All derivatives of T3 studied were deiodinated by hepatic type I MD more avidly than the parent iodothyronine. Our data suggest that 1) deamination does not appreciably influence, while sulfoconjugation markedly inhibits type III 5-monodeiodination of T3; and 2) deamination may be even more conducive to degradation of thyroid hormone than sulfoconjugation.

Animals↗
PubMed1991

Proton editing and imaging of lactate.

Highly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor-sensitizers. The methods (GE-DQCOSY and GE-HMQC) may be particularly useful in heteronuclear NMR in vivo.

Animals↗