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Biomedical subjects

R Reddy

Publications and source records attributed to R Reddy.

At least 37 records · Page 2Linked to original sources

Human knee: in vivo T1(rho)-weighted MR imaging at 1.5 T--preliminary experience.

A fast spin-echo sequence weighted with a time constant that defines the magnetic relaxation of spins under the influence of a radio-frequency field (T1(rho)) was used in six subjects to measure magnetic resonance (MR) relaxation times in the knee joint with a 1.5-T MR imager. A quantitative comparison of T2- and T1(rho)-weighted MR images was also performed. Substantial T1(rho) dispersion was demonstrated in human articular cartilage, but muscle did not demonstrate much dispersion. T1(rho)-weighted images depicted a chondral lesion with 25% better signal-difference-to-noise ratios than comparable T2-weighted images. This technique may depict cartilage and muscular abnormalities.

Adult↗

Invited response

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Journal Article↗

Abnormal age-related changes of plasma antioxidant proteins in schizophrenia.

Albumin and bilirubin are metal-binding proteins, shown to possess free radical scavenging properties, and may thus be selective antioxidants. In the present study we examined whether individual plasma antioxidants such as albumin and bilirubin, which significantly contribute to total antioxidant status (TAS), are reduced in patients with schizophrenia. We prospectively studied plasma antioxidant proteins, i.e. albumin and bilirubin, in male veteran schizophrenic patients using a within-subject, repeated measures, on-off-on haloperidol treatment design, as well as age- and sex-matched healthy volunteers. Male patients with schizophrenia either during haloperidol treatment (n=46) or in a drug-free condition (n=35) had significantly lower levels of both plasma albumin and bilirubin compared with age- and sex-matched healthy volunteers (n=31). Such reductions of plasma antioxidant proteins in schizophrenic patients appear to be age-related changes, in contrast to those observed in healthy volunteers. On the other hand, levels of plasma albumin and bilirubin were not significantly affected by haloperidol treatment, haloperidol withdrawal, or length of drug-free period. Moreover, plasma TAS was not influenced significantly by cigarette smoking, even though it may selectively decrease plasma bilirubin but not albumin levels. The present findings, taken together with our previous results of reduced plasma TAS and uric acid, as well as an increased Red blood cell superoxide dismutase, lend further support to the hypothesis that a defect in the antioxidant defense system exists in schizophrenia that may lead to oxidative damage.

Adolescent↗

Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc.

Unlike normal mammalian cells, which use oxygen to generate energy, cancer cells rely on glycolysis for energy and are therefore less dependent on oxygen. We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism. In Rat1a fibroblasts and murine livers overexpressing c-Myc, the mRNA levels of the glucose transporter GLUT1, phosphoglucose isomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase were elevated. c-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.

Animals↗

Demonstration of a compact compressor for application of metastability-exchange optical pumping of 3He to human lung imaging.

Hyperpolarized gas magnetic resonance imaging has recently emerged as a method to image lungs, sinuses, and the brain. The best lung images to date have been produced using hyperpolarized 3He, which is produced by either spin-exchange or metastability-exchange optical pumping. For hyperpolarized gas MRI, the metastable method has demonstrated higher polarization levels and higher polarizing rates, but it requires compression of the hyperpolarized gas. Prior to this work, compression of hyperpolarized gas had only been accomplished using a large, complex and expensive apparatus. Here, human lung ventilation images are presented that were obtained using a compact compressor that is relatively simple and inexpensive. For this test, 1.1 bar-L of 15% hyperpolarized 3He gas was produced at the National Institute of Standards and Technology using a modified commercial diaphragm pump. The hyperpolarized gas was transported to the University of Pennsylvania in a holding field provided by a portable solenoid.

Adult↗

Sodium visibility and quantitation in intact bovine articular cartilage using high field (23)Na MRI and MRS.

Noninvasive methods of detecting cartilage degeneration can have an impact on identifying the early stages of osteoarthritis. Accurate measurement of sodium concentrations within the cartilage matrix provides a means for analyzing tissue integrity. Here a method is described for quantitating sodium concentration and visibility in cartilage, with general applications to all tissue types. The sodium concentration in bovine patellar cartilage plugs was determined by three different methods: NMR spectroscopy of whole cartilage plugs, NMR spectroscopy of liquefied cartilage in concentrated HCl, and inductively coupled plasma emission spectroscopy. Whole bovine patellae were imaged with relaxation normalized calibration phantoms to ascertain sodium concentrations inside the articular cartilage. Sodium concentrations in intact articular cartilage were found to range from approximately 200 mM on the edges to approximately 390 mM in the center, with an average of approximately 320 mM in five separate bovine patellae studied. In essence, we have created sodium distribution maps of the cartilage, showing for the first time, spatial variations of sodium concentration in intact cartilage. This average concentration measurement correlates very well with the values obtained from the spectroscopic methods. Furthermore, sodium was found to be 100% NMR visible in cartilage plugs. Applications of this method in diagnosing and monitoring treatment of osteoarthritis are discussed.

Animals↗

Time-domain quantification of multiple-quantum-filtered (23)Na signal using continuous wavelet transform analysis.

The application of continuous wavelet transform (CWT) analysis technique is presented to analyze multiple-quantum-filtered (MQF) (23)Na magnetic resonance spectroscopy (MRS) data. CWT acts on the free-induction-decay (FID) signal as a time-frequency variable filter. The signal-to-noise ratio (SNR) and frequency resolution of the output filter are locally increased. As a result, MQF equilibrium longitudinal magnetization and the apparent fast and slow transverse relaxation times are accurately estimated. A developed iterative algorithm based on frequency signal detection and components extraction, already proposed, was used to estimate the values of the signal parameters by analyzing simulated time-domain MQF signals and data from an agarose gel. The results obtained were compared to those obtained by measurement of signal height in frequency domain as a function of MQF preparation time and those obtained by a simple time-domain curve fitting. The comparison indicates that the CWT approach provides better results than the other tested methods that are generally used for MQF (23)Na MRS data analysis, especially when the SNR is low. The mean error on the estimated values of the amplitude signal and the apparent fast and slow transverse relaxation times for the simulated data were 2.19, 6. 63, and 16.17% for CWT, signal height in frequency domain, and time-domain curve fitting methods, respectively. Another major advantage of the proposed technique is that it allows quantification of MQF (23)Na signal from a single FID and, thus, reduces the experiment time dramatically.

Magnetic Resonance Spectroscopy↗

17O-decoupled (1)H spectroscopy and imaging with a surface coil: STEAM decoupling.

(17)O-decoupled (1)H spin-echo imaging has been reported as a means of indirect (17)O detection, with potential application to measurement of blood flow and metabolism. In its current form, (17)O decoupling requires large RF amplitudes and a 180 degrees refocusing pulse, complicating its application in volume and surface coils, respectively. To overcome this problem, we have developed an (17)O-decoupled proton stimulated echo sequence ("STEAM decoupling") to allow (17)O detection with a surface coil. A high B(1) amplitude is easily generated, allowing complete decoupling of (17)O and (1)H. Slice-selective, (17)O-decoupled (1)H imaging is readily performed and the sequence is easily adapted for localized spectroscopy. Intrinsic correction for variations in B(1) and further compensation for B(1) inhomogeneity are discussed.

Animals↗

Temperature-dependent chemical shift and relaxation times of (23)Na in Na(4)HTm[DOTP].

We describe the characterization of a (23)Na temperature-dependent chemical shift and relaxation rates in the complex, Na(4)HTm[DOTP]. This is the first characterization of a (23)Na temperature-dependent chemical shift in a nonmetallic sample. The (23)Na temperature-dependent chemical shift coefficient is approximately -0. 5 PPM/ degrees C for both an aqueous solution and a 6% agarose gel of this compound. This is 50 times the magnitude of the temperature-dependent chemical shift coefficient of water protons. The relaxation times, T(1), T(2f), and T(2s) increased by 0.1, 0.01, and 0.05 ms/ degrees C, respectively. Applications of these unique properties for designing an MRI technique for monitoring heat deposition in tissue and tissue phantoms are discussed.

Gels↗

Intermolecular dipole-dipole relaxation of (129)Xe dissolved in water.

Intermolecular (129)Xe-(1)H nuclear Overhauser effects and (129)Xe longitudinal relaxation time measurements were used to demonstrate that the dipole-dipole coupling is the dominant relaxation mechanism for (129)Xe in water, at room temperature. (129)Xe-(1)H cross-relaxation rates were derived to be sigma(XeH) approximately 3.2 +/- 0.3 x 10(-3) s(-1), independent of xenon pressure (in the range of 1-10 bar) and of the presence of oxygen. Corresponding xenon-proton internuclear distances were calculated to be 2.69 +/- 0.12 A. Using the magnitude of the dipole-dipole coupling and the spin density ratio between dissolved xenon and bulk water, it is estimated that (129)Xe-(1)H spin polarization-induced nuclear Overhauser effects would yield little net proton signal enhancement in water.

Algorithms↗

MR imaging of RF heating using a paramagnetic doped agarose phantom.

In this paper, we present the first description of a technique to visualize and quantitate radiofrequency (RF) heating of a tissue phantom during a magnetic resonance imaging (MRI) procedure. We evaluated the heating patterns of four 10 cm diameter transmit/receive surface coils with differing degrees of distributed capacitance. The tissue phantom was a 6% agarose gel doped with 40 mM Na(4)HTm[DOTP], and possesses a conductivity intermediate to human muscle and fat. Heating was discerned via phase difference mapping using the large temperature dependent chemical shift coefficient for 23Na in Na(4)HTm[DOTP]. This coefficient is -0.5 ppm/ degrees C. Heating was highest where the phantom was closest to the surface coils, dropping off towards the center of the coil. No significant difference was observed in the heating patterns between the different surface coils. For the experimental setups used in this study, electric field 'hot spots' at the areas corresponding to the placement of the capacitor gaps were not observed.

Biophysical Phenomena↗

Radical resection of periampullary tumors in the elderly: evaluation of long-term results.

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65-87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 +/- 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients > or =75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.

Adenocarcinoma↗

A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B.

BACKGROUND/AIMS: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 microg/kg b.w., n=15; 0.25 microg/kg b.w., n=15; 0.50 microg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. METHODS: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. RESULTS: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 microg/kg b.w. (25%) or with 0.25 microg/kg b.w. (13%) compared with those given 0.03 microg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25microg/kg (2/15) or the 0.50 microg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-gamma, IL-10, neopterin and beta2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. CONCLUSIONS: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.

Adjuvants, Immunologic↗

Effect of 3' terminal adenylic acid residue on the uridylation of human small RNAs in vitro and in frog oocytes.

It is known that several small RNAs including human and Xenopus signal recognition particle (SRP) RNA, U2 small nuclear RNA (snRNA) and 7SK RNAs are posttranscriptionally adenylated, whereas U6 snRNA and ribosomal 5S RNA are posttranscriptionally uridylated on their 3' ends. In this study, we provide evidence that a small fraction of U6 snRNA and 5S ribosomal RNA molecules from human as well as Xenopus oocytes contain a single posttranscriptionally added adenylic acid residue on their 3' ends. These data show that U6 snRNA and 5S rRNAs are posttranscriptionally modified on their 3' ends by both uridylation and adenylation. Although the SRP RNA, 7SK RNA, 5S RNA, and U6 snRNA with the uridylic acid residue on their 3' ends were readily uridylated, all these RNAs with posttranscriptionally added adenylic acid residue on their 3' ends were not uridylated in vitro, or when U6 snRNA with 3' A(OH) was injected into Xenopus oocytes. These results show that the presence of a single posttranscriptionally added adenylic acid residue on the 3' end of SRP RNA, U6 snRNA, 5S rRNA, or 7SK RNA prevents 3' uridylation. These data also show that adenylation and uridylation are two competing processes that add nucleotides on the 3' end of some small RNAs and suggest that one of the functions of the 3' adenylation may be to negatively affect the 3' uridylation of small RNAs.

Adenosine Monophosphate↗

Evolutionary conservation of post-transcriptional 3' end adenylation of small RNAs: S. cerevisiae signal recognition particle RNA and U2 small nuclear RNA are post-transcriptionally adenylated.

The 3' terminal nucleotide of several human small RNAs, including Signal Recognition Particle (SRP) RNA, 7SK RNA, U2 small nuclear RNA and ribosomal 5S RNA was previously characterized and a fraction of these RNAs was found to contain a single post-transcriptionally added adenylic acid residue on their 3' ends. Here we report the development of a reverse transcription-polymerase chain reaction (RT-PCR) assay for determining and quantifying the extent of post-transcriptional adenylation of RNAs from different species. Using this assay, we found that a fraction of S. cerevisiae U2 small nuclear RNA and S. cerevisiae SRP RNA contain a post-transcriptionally added adenylic acid residue on their 3' ends. Sequencing analysis confirmed this adenylation to be post-transcriptional. Corresponding small RNAs in Xenopus oocytes also contained this post-transcriptional adenylation on their 3' ends. These data show that post-transcriptional adenylation on the 3' end of several small RNA molecules is conserved through evolution. Xenopus SRP RNA from both cytoplasmic and nuclear compartments contained post-transcriptionally added adenylic acid residue on its 3' end. In addition, the Alu portion of SRP RNA was adenylated, when injected into the cytoplasm of frog oocytes. These data show that this novel adenylating machinery, capable of specifically adding a single adenylic acid to the 3' end of some RNA molecules, is present and functional in both nucleus and cytoplasm.

Adenosine Monophosphate↗

Identification of a approximately 30S size non-ribosomal Saccharomyces cerevisiae RNA that is rapidly labeled on its 3' end by ATP or UTP.

Cell-free extracts prepared from S. cerevisiae cells were incubated in the presence of [alpha-32P]-labeled ATP, CTP, GTP or UTP. An RNA larger than ribosomal 25S RNA with an apparent size of approximately 30S was prominently labeled on its 3' end in the presence of ATP or UTP but not with CTP or GTP. This labeled RNA was not hybrid-selected by cloned yeast ribosomal DNA; in addition, this approximately 30S RNA was not cleaved by RNase H in the presence of complementary deoxyribooligonucleotides to rRNA. These two lines of evidence show that this approximately 30S RNA is not structurally related to ribosomal RNA gene repeat. The cell-free extracts prepared from yeast cells containing temperature-sensitive poly(A) polymerase adenylated this novel yeast RNA at restrictive temperature with efficiency similar to extracts prepared from wild-type yeast cells. These data show that the enzyme responsible for adenylation of this approximately 30S RNA is distinct from mRNA poly(A) polymerase. While the human SRP RNA 3' adenylating enzyme in the HeLa cell extract adenylated human SRP or Alu RNAs, the yeast adenylating enzyme did not adenylate the human SRP or Alu RNAs in vitro; these data indicate species specificity for this adenylating enzyme.

Adenosine Triphosphate↗