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Biomedical subjects

D Burstein

Publications and source records attributed to D Burstein.

At least 37 records · Page 2Linked to original sources

Body cavity-based malignant lymphoma containing Kaposi sarcoma-associated herpesvirus in an HIV-negative man with previous Kaposi sarcoma.

BACKGROUND: The role of Kaposi sarcoma-associated herpesvirus in the development of malignant lymphomas in patients negative for the human immunodeficiency virus (HIV) has not been established. OBJECTIVE: To examine the possible role of Kaposi sarcoma-associated herpesvirus in a case of body cavity-based malignant lymphoma that occurred in an HIV-negative patient who had previously had Kaposi sarcoma. DESIGN: Case study. SETTING: Academic medical center. PATIENT: A 94-year-old man with lymphomatous ascites. MEASUREMENTS: Polymerase chain reaction (PCR) and Southern blot DNA analysis. RESULTS: The body cavity-based lymphoma cells were positive for Kaposi sarcoma-associated herpesvirus by PCR and were negative for other herpesviruses, including Epstein-Barr virus, cytomegalovirus, and human herpesviruses 6 and 7. Southern blot analysis of lymphoma DNA showed high levels of Kaposi sarcoma-associated herpesvirus (> 40 to 80 genomes/cell). Clonal rearrangement of the immunoglobulin JH and JK genes was present, confirming the presence of a clonal B-cell proliferation. CONCLUSIONS: Kaposi sarcoma-associated herpesvirus may be involved in the development of malignant lymphoma after Kaposi sarcoma in HIV-negative patients. This type of lymphoma, in contrast to body cavity-based lymphoma related to the acquired immunodeficiency syndrome, may have an indolent clinical course.

Aged↗

Gd-DTPA2- as a measure of cartilage degradation.

Glycosaminoglycans (GAGs) are the main source of tissue fixed charge density (FCD) in cartilage, and are lost early in arthritic diseases. We tested the hypothesis that, like Na+, the charged contrast agent Gd-DTPA2- (and hence proton T1) could be used to measure tissue FCD and hence GAG concentration. NMR spectroscopy studies of cartilage explants demonstrated that there was a strong correlation (r > 0.96) between proton T1 in the presence of Gd-DTPA2- and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equilibrium model was examined as a means of quantifying FCD from Gd-DTPA2- concentration, yielding a value 50% less but linearly correlated with the validated method of quantifying FCD from Na+. These data could be used as the basis of an empirical model with which to quantify FCD from Gd-DTPA2- concentration, or a more sophisticated physical model could be developed. Spatial distributions of FCD were easily observed in T1-weighted MRI studies of trypsin and interleukin-1 induced cartilage degradation, with good histological correlation. Therefore, equilibration of the tissue in Gd-DTPA2- gives us the opportunity to directly image (through T1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical studies demonstrated Gd-DTPA2- penetration into cartilage, suggesting that this technique is clinically feasible.

Animals↗

Magnetization transfer in cartilage and its constituent macromolecules.

The goal of this work was to investigate magnetization transfer (MT) in cartilage by measuring water proton signals Ms/Mo, as an indicator of MT, in (i) single-component systems of the tissue's constituent macromolecules and (ii) intact cartilage under control conditions and after two pathomimetic interventions. Ms/Mo was quantified with a 12-microT saturation pulse applied 6 kHz off resonance. Both glycosaminoglycans (GAG) and collagen exhibited concentration dependent effects on Ms/Mo, being approximately linear for GAG solutions (Ms/Mo = -0.0137[% GAG] + 1.02) and exponential for collagen suspensions (Ms/Mo = 0.80 x exp[-(%collagen)/6.66] + 0.20); the direct saturation of water could not account for the measured Ms/Mo. Although the effect of collagen on Ms/Mo is much stronger than for a corresponding concentration of GAG, Ms/Mo is not very sensitive to changes in collagen concentration in the physiological range. Tissue degradation with 25 mg/ml trypsin led to an increase in Ms/Mo from the baseline value of 0.2 (final/initial values = 1.15 +/- 0.13, n = 11, P < 0.001). In contrast, a 10-day treatment of cartilage with 100 ng/ml of interleukin-1 beta (IL-1 beta) caused a 19% decrease in Ms/Mo (final/initial values = 0.81 +/- 0.08, n = 3, P = 0.085). The changes in hydration and macromolecular content for the two treatments were comparable, suggesting that Ms/Mo is sensitive to macromolecular structure as well as concentration. In conclusion, whereas the baseline Ms/Mo value in cartilage may be primarily due to the tissue collagen concentration, changes in Ms/Mo may be due to physiological or pathophysiological changes in GAG concentration and tissue structure, and the measured Ms/Mo may differentiate between various pathomimetic degradative procedures.

Animals↗

Studies of Gd-DTPA relaxivity and proton exchange rates in tissue.

The image intensity in many contrast agent perfusion studies is designed to be a function of bulk tissue T1, which is, in turn, a function of the compartmental (vascular, interstitial, and cellular) T1s, and the rate of proton exchange between the compartments. The goal of this study was to characterize the compartmental tissue Gd-DTPA relaxivities and to determine the proton exchange rate between the compartments. Expressing [Gd-DTPA] as mmol/liter tissue water, the relaxivities at 8.45 T and room temperature were: saline, 3.87 +/- 0.06 (mM.s)-1 (mean +/- SE; n = 29); plasma, 3.98 +/- 0.05 (mM.s)-1 (n = 6); and control cartilage (primarily an interstitium), 4.08 +/- 0.08 (mM.s)-1 (n = 17), none of which are significantly different. The relaxivity of cartilage did not change with compression, trypsinization, or equilibration in plasma, suggesting relaxivity is not influenced by interstitial solid matrix density, charge, or the presence of plasma proteins. T1 relaxation studies on isolated perfused hearts demonstrated that the cellular-interstitial water exchange rate is between 8 and 27 Hz, while the interstitial-vascular water exchange rate is less than 7 Hz. Thus, for Gd-DTPA concentrations, which would be used clinically, the T1 relaxation rate behavior of intact hearts can be modeled as being in the fast exchange regime for cellular-interstitial exchange but slow exchange for interstitial-vascular exchange. A measured relaxivity of 3.82 +/- 0.05 (mM.s)-1 (n = 8) for whole blood (red blood cells and plasma) and 4.16 +/- 0.02 (mM.s)-1 (n = 3) for frog heart tissue (cells and interstitium) (with T1 and Gd-DTPA concentration defined from the total tissue water volume) supports the conclusion of fast cellular-extracellular exchange. Knowledge of the Gd-DTPA relaxivity and maintaining Gd-DTPA concentration in the range so as to maintain fast cellular-interstitial exchange allows for calculation of bulk Gd-DTPA concentration from bulk tissue T1 within a calculable error due to slow vascular exchange.

Animals↗

Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging.

The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2 s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na+, Li+, and CF3CO2-) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of -300 mM at pH 8 becomes approximately -50 mM at pH 2) did not affect the diffusivity of water or Na+. These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li+ dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion-weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D2O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

MRI evaluation of myocardial perfusion without a contrast agent using magnetization transfer.

We propose a new magnetic resonance imaging (MRI) technique that is sensitive to myocardial tissue perfusion that obviates the use of an extrinsic contrast agent. Significant advantages of such a technique are that it avoids accumulation of contrast agent when repeated studies are performed on the same subject and that it is completely noninvasive. The method makes use of a combination of magnetization transfer (MT) and T1sat (measured spin-lattice relaxation time in the presence of MT) weighting. In this Communication, we present observations from experiments with an isolated rat heart model that demonstrate increase of MT-weighted signal intensity and T1sat with flow. Also included are data showing that these effects can be made synergistic for enhancing the sensitivity to perfusion. We have observed about a 3% change in MT-weighted intensity and up to 10% change in MTT1sat-weighted intensity for a change of 1 ml/min in global flow rate.

Animals↗

Determination of fixed charge density in cartilage using nuclear magnetic resonance.

Many biomechanical and chemical properties of cartilage are dependent on the fixed charge density (FCD) of the extracellular matrix. In this study, nuclear magnetic resonance (NMR) spectroscopy was investigated as a nondestructive technique for determining FCD in cartilage. Sodium content was measured by NMR in cartilage explants and was compared with sodium content measured by inductively coupled plasma emission spectroscopy (ICP) in order to verify the total NMR visibility of sodium in cartilage. The ratio of NMR to ICP results was 1.02 +/- 0.04 (calf, mean +/- SD, n = 7) and 1.04 +/- 0.11 (adult bovine, n = 8). Sodium concentration as measured by NMR was then used with ideal Donnan theory to compute estimates of FCD. For calf articular cartilage (AC) near physiological conditions, calculated FCD was -0.28 +/- 0.03 M (n = 10). NMR measurements were then made for individual cartilage specimens sequentially equilibrated in baths of differing salt composition, pH, or ionic strength. For calf and adult AC, calculated FCD decreased dramatically between pH 3 and 2, with adult specimens becoming positively charged but calf tissue retaining a net negative charge. For calf AC equilibrated in 0.3-0.015 M NaCl, calculated FCD was observed to decrease slightly with decreasing bath ionic strength. For epiphyseal cartilage, FCD varied with the position of origin of the explant within the joint, ranging from -0.19 to -0.35 M in a manner that correlated with tissue glycosaminoglycan content. Preliminary NMR imaging experiments demonstrated similar variations of sodium concentration in intact ulnar epiphyseal cartilage. Collectively, these results demonstrate the ability of NMR to nondestructively follow FCD in cartilage. The technique is applicable to dynamic studies as well as to both in vitro and in vivo studies on living tissue.

Animals↗

Characteristics of extracellular sodium relaxation in perfused hearts with pathologic interventions.

Sodium spectroscopy and imaging sequences designed to emphasize fast T2 decay or the multiple quantum signal have previously demonstrated a high contrast between normal and pathologic tissue which may be due to changes in intracellular versus extracellular sodium distribution. Since alterations in the amount of signal with fast T2 decay have previously been shown to occur with changes in intracellular sodium content, this study investigated the fast T2 relaxation characteristics of extracellular sodium during pathologic interventions on nonsubmerged perfused rat hearts. T2 data on total sodium content were obtained while global ischemia (stopping all perfusate flow) and extracellular edema (due to long perfusion times) were induced in the heart. The data were fit to a biexponential, with Mf(T2f) the magnitude (time constant) of the fast component of decay. Mf increased significantly in both pathologies (to 319 +/- 26%, n = 3, of baseline for ischemia and to 527 +/- 284%, n = 3, of baseline for edema); the increase with edema was demonstrated to be due to extracellular sodium by intermittently perfusing the heart for a short period with shift reagent. When shift reagent was not used until the conclusion of the edema experiment, Mf increased to 169 +/- 35% of baseline, also due mainly to extracellular sodium. T2f did not exhibit any trends with these experiments, with values ranging from 1.7 to 5.5 ms. We believe that these results indicate that compartmental sodium content will most likely not be quantifiable in pathologic states in the heart with relaxation-based techniques. However, correlations between the pathologic state of the tissue and the sodium NMR signal obtained with pulse sequences or images that emphasize a particular aspect of relaxation may prove to be useful.

Animals↗

Factors in myocardial "perfusion" imaging with ultrafast MRI and Gd-DTPA administration.

Ultrafast magnetic resonance imaging (MRI) and first pass observation of an interstitial contrast agent are currently being used to study myocardial perfusion. Image intensity, however, is a function of several parameters, including the delivery of the contrast agent to the interstitium (coronary flow rate and diffusion into the interstitium) and the relaxation properties of the tissue (contrast agent concentration, proton exchange rates, and relative intra- and extracellular volume fractions). In this study, image intensity during gadopentetate dimeglumine (Gd-DTPA) administration with T1-weighted ultrafast MR imaging was assessed in an isolated heart preparation. With increasing Gd-DTPA concentration, the steady-state myocardial image intensity increased but the time to reach steady state remained unchanged, resulting in an increased slope of image intensity change. A range of physiologic perfusion pressures (and resulting coronary flow rates) had insignificant effects on kinetics of Gd-DTPA wash-in or steady-state image intensity, suggesting that diffusion of Gd-DTPA into the interstitium is the rate limiting step in image intensity change with this preparation. Following global ischemia and reperfusion, transmural differences in the slope of image intensity change were apparent. However, the altered steady-state image intensity (due to postischemic edema) makes interpretation of this finding difficult. The studies described here demonstrate that although Gd-DTPA administration combined with ultrafast imaging may be a sensitive indicator of perfusion abnormalities, factors other than perfusion will affect image intensity. Extensive studies will be required before image intensity with this protocol is fully understood.

Animals↗

Coronary arteries: breath-hold MR angiography.

The authors describe a method for performance of ultrafast magnetic resonance (MR) angiography of coronary arteries with a standard clinical MR system and a body coil. Each image was obtained within a single breath hold by using an electrocardiography-gated, segmented, ultrafast, gradient-echo pulse sequence with an incremental excitation flip angle for the eight phase-encoding steps acquired per segment. By using overlapping 4-mm-thick sections, the coronary arteries were routinely depicted from the coronary ostia distally at MR in healthy subjects. Ultrafast MR angiography of the coronary arteries is feasible with use of a standard body coil. This technique offers considerable potential as an investigational tool and, with further development, may become a clinically useful imaging application.

Adult↗

Nuclear magnetic resonance studies of sodium/calcium exchange in frog perfused, beating hearts.

This study explores the effect of extracellular Ca2+ concentration ([Ca2+]o), on the intracellular Na+ concentration ([Na+]i), in frog intact hearts using nuclear magnetic resonance spectroscopy, which allows for the measurement of [Na+]i in perfused, beating hearts. Decreases in [Ca2+]o yielded marked increases in [Na+]i. A similar effect was seen during inhibition of the Na+/K+ pump and was fully reversible. This sensitivity of [Na+]i to [Ca2+]o, previously observed using microelectrodes, supports a crucial physiological role for Na+/Ca2+ exchange in frog intact, beating hearts.

Animals↗

Interstitial sodium nuclear magnetic resonance relaxation times in perfused hearts.

Separation of intracellular and extracellular sodium nuclear magnetic resonance (NMR) signals would enable nondestructive monitoring of intracellular sodium. It has been proposed that differences between the relaxation times of intracellular and extracellular sodium be used either directly or indirectly to separate the signal from each compartment. However, whereas intracellular sodium relaxation times have been characterized for some systems, these times were unknown for interstitial sodium. In this study, the interstitial sodium NMR relaxation times have been measured in perfused frog and rat hearts under control conditions. This was achieved by eliminating the NMR signal from the extracardiac (perfusate) sodium, and then quantifying the remaining cardiac signal. The intracellular signal was measured to be 8% (frog) or 22% (rat) of the cardiac signal and its subtraction was found to have a negligible effect on the cardiac relaxation times. Therefore this cardiac signal is considered to provide a good estimate of interstitial relaxation behavior. For perfused frog (rat) hearts under control conditions, this signal was found to have a T1 of 31.6 +/- 3.0 ms (27.3 +/- 1.6 ms) and a biexponential T2 of 1.9 +/- 1.0 ms (2.1 +/- 0.3 ms) and 25.2 +/- 1.3 ms (26.3 +/- 3.2 ms). Due to the methods used to separate cardiac signal from perfusate signal, it is possible that this characterized only a part of the signal from the interstitium. The short T2 component attributable to the interstitial signal indicates that separation of the NMR signals from each compartment on the basis of relaxation times alone may be difficult.

Animals↗

First-pass cardiac perfusion: evaluation with ultrafast MR imaging.

The authors studied cardiac perfusion by administering gadolinium diethylenetriaminepentaacetic acid (DTPA) in conjunction with an ultrafast imaging technique that produces strongly T1-weighted images. The method consisted of a 180 degrees inversion pulse, followed by a gradient-echo acquisition with a very short repetition time (less than 4 msec). Each image was acquired throughout a small fraction of the cardiac cycle. The method was applied in an isolated perfused rat heart model (acquisition time = 116 msec) and in human subjects without known cardiac disease (acquisition time = 125 msec). Fast, high-resolution images (128 X 128 matrix) were created by combining sequentially acquired small matrixes. After bolus administration of Gd-DTPA in the perfused rat heart model, contrast was pronounced between the nonperfused myocardium and perfused normal myocardium. First-pass wash-in and washout phases of the contrast material were observed in the perfused rat heart model and in human subjects. Results demonstrated the clinical feasibility of first-pass perfusion studies of the heart. The studies can be performed on a conventional whole-body imaging system with standard hardware.

Animals↗

Measurement of left ventricular mass in rats using electrocardiogram-gated magnetic resonance imaging.

To evaluate the ability of electrocardiogram (ECG)-gated magnetic resonance (MR) imaging to assess in vivo left ventricular (LV) mass in the rat, we studied 20 healthy adult Sprague-Dawley and Fischer 344 rats and 8 additional rats that underwent scanning after induction of volume overload by aortic leaflet disruption. ECG-gated spin-echo pulse sequences were used to acquire a series of 1-mm thick modified short-axis images of the left ventricle. The area enclosed by the endocardial and epicardial borders of the left ventricle was multiplied by the interslice distance and specific gravity of myocardium to obtain calculated slice mass. Total LV mass was obtained by summing the individual slices. The calculated value for LV mass was then compared with the LV mass as determined at postmortem examination. Linear regression analysis showed an excellent correlation of MR-estimated mass (x) with autopsy-measured LV mass (y) (y = 0.90x + 65, r = 0.98). For this method intraobserved and interobserver slice correlations were 0.97 and 0.96, respectively. There was no significant difference in LV mass as determined from a series of diastolic vs. systolic images in a subset of six animals. Over a mean of 6.5 wk of observation, LV mass increased by 40% in the animals subjected to aortic leaflet disruption. These results demonstrate that MR imaging is highly accurate for the non-invasive in vivo assessment of LV mass in the adult rat.

Animals↗

Parvovirus B19-associated hemophagocytic syndrome.

Parvovirus B19 is a recently described pathogen, associated with an increasing spectrum of clinical manifestations. We present the first reported case, to our knowledge, of parvovirus B19-associated hemophagocytic syndrome, in which the diagnosis of parvovirus infection was documented by the presence of B19-specific IgM and IgG antibodies. Pancytopenia resolved immediately following splenectomy and the patient recovered completely.

Antibodies, Viral↗

NMR characteristics of "visible" intracellular myocardial potassium in perfused rat hearts.

Nuclear magnetic resonance (NMR) spectroscopy provides a unique view of ions through its noninvasive character and relaxation time measurements. Several previous studies have demonstrated that only approximately 20% of cardiac intracellular potassium is visible with current NMR techniques. This study investigates the NMR visible intracellular potassium in a perfused rat heart preparation. When shift reagents were used to separate the intra- and extracellular signals, an intracellular T1 of 11.8 +/- 0.6 ms, and an intracellular T2 with two time constants of 1.3 +/- 0.6 ms (33 +/- 8%) and 10.1 +/- 1.9 ms (67 +/- 4%) were measured. Curve stripping techniques used to separate the intra- and extracellular components of a bulk relaxation decay yielded an intracellular T1 of 8.4 +/- 0.3 ms and an intracellular T2 with two time constants of 1.1 +/- 0.6 ms (38 +/- 10%) and 8.0 +/- 1.6 ms (62 +/- 12%). These results demonstrate that there are at least two distinct pools of potassium within the cardiac cell in slow exchange with each other on the NMR time scale. Studies with an enriched 41K perfusate demonstrated that the exchange rate for the visible intra- and extracellular potassium is on the order of 15 min.

Animals↗

Prevention of diabetes in BB/Wor rat by single transfusion of spleen cells. Parameters that affect degree of protection.

Previous studies have shown that multiple transfusions of spleen cells from histocompatible nondiabetic donors prevent autoimmune diabetes mellitus in diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) rats. In this study, a single transfusion of greater than or equal to 50 x 10(6) cells from either diabetes-resistant (DR) BB/Wor or Wistar-Furth (WF) rats substantially reduced the incidence of diabetes when given to DP rats 27 or 46 days old but not 61 days old. Transfusion and protection were associated with the appearance of RT6+ donor lymph node cells in recipient rats. In vivo depletion of RT6+ T-lymphocytes in 150-day-old protected animals did not produce diabetes. DR BB/Wor and WF spleen cells were equally efficacious when given either intraperitoneally or intravenously. Mitogen-activated spleen cells were relatively less effective than untreated cells. We conclude that BB rat diabetes can be prevented by one transfusion of spleen cells from histocompatible DR and WF donors, and that the protective effect is dependent on recipient age and cell dose. The effect may be mediated by a population of RT6+ T-lymphocytes that, during a critical developmental period, regulate the expression of autoimmunity in these animals.

Age Factors↗