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Biomedical subjects

T E Merchant

Publications and source records attributed to T E Merchant.

At least 73 records · Page 4Linked to original sources

Quantitative changes in tumor metabolism, partial pressure of oxygen, and radiobiological oxygenation status postradiation.

Hypoxia is considered to be a major cause of tumor radioresistance. Reoxygenation of previously hypoxic areas after a priming dose of radiation is associated with an increase in tumor radiosensitivity. In a study of a hypoxic mammary carcinoma, 31P nuclear magnetic resonance spectra showed statistically significant increases in metabolite ratios (phosphocreatine/Pi and nucleotide triphosphate/Pi) after 65 and 32 Gy. The maximum changes in metabolite ratios after 32 Gy occurred at 48 h, although significant changes were detected at 24 h. A corresponding increase in the mean tumor pO2 (polarographic microelectrode measurements) and a decrease in hypoxic cell fraction [changes in paired (clamped versus unclamped) tumor control dose for 50% of tumors] were also shown to occur 48 h after a priming dose of 32 Gy. A significant increase in the mean tumor pO2, phosphocreatine/Pi, and nucleotide triphosphate/Pi, compared to initial values, was noted at 24, 48, and 96 h post 65-Gy radiation. An increase in the downfield component of the phosphomonoester peak relative to the upfield component (phosphoethanolamine), is also noted after doses of 65 and 32 Gy. These are likely to be due to cell kill and/or decreased cell proliferation. In this tumor model, 31P nuclear magnetic resonance spectroscopic changes postradiation are temporally coincident with and may be indicative of tumor reoxygenation as measured by the tumor control dose for 50% of tumors and oxygen-sensitive microelectrodes.

Animals↗

Phosphodiesters in saponified extracts of human breast and colon tumors using 31P magnetic resonance spectroscopy.

Saponified phospholipid extracts of malignant and normal human breast and colon surgical tissue specimens (n = 45) generate characteristic phosphodiester profiles using 31P magnetic resonance (MR) spectroscopy. The resultant 31P MR spectroscopic profiles of the analyzed tissues are used to differentiate malignant from normal. The appearance of an uncharacterized resonance at 0.29 delta in the malignant tissue spectra (50% of breast and 75% of colon specimens) is the most notable qualitative finding. Quantitatively, malignant colon tissues differ from normal colon tissues with depressed levels of phosphatidylserine and elevated levels of glycerol 3-phosphorylglycerol and an index measuring the summation of phospholipid polar head group residues with free hydroxyl groups. Malignant breast tissues have significantly elevated levels of glycerol 3-phosphorylethanolamine and significantly depressed levels of glycerol 3-phosphorylcholine compared to normal breast tissues, reflecting a perturbation in the balance of lipid residues that are the respective breakdown products of phosphatidylethanolamine and phosphatidylcholine. The concentration of the polar head group residues is compared to 31P MR spectroscopic profiles of colon and breast tissue phospholipids, in order to demonstrate the quantitative nature of the technique employed.

Adenocarcinoma↗

31P NMR of tissue phospholipids: competition for Mg2+, Ca2+, Na+ and K+ cations.

Phosphatidylcholine (PC), phosphatidylethanolamine (PE), ethanolamine plasmalogen (EPLAS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin (CL), phosphatidylglycerol (PG) and phosphatidic acid (PA) were dispersed together in Cs(ethylenedinitrilo)tetraacetic acid-scrubbed chloroform/methanol solution, and high resolution 31P nuclear magnetic resonance spectra were recorded. In separate titration experiments, Mg2+ and Ca2+ were added to the dispersed phospholipid mixture to determine the relative interaction potentials of each of the phospholipids for each of the added cations. The association of cations with individual phospholipids was indicated by 31P chemical-shift changes, signal broadening, signal quenching or a combination of these. The titrations revealed that CL had the highest, and PA the next highest, interaction potential for Mg2+ cations. In contrast, PS and PA had the highest, and CL the next highest, interaction potential for Ca2+. Considering only interactions with Ca2+ ions, the phospholipids can be divided into three distinct groups: PS and PA (high interaction potential); CL, PI and PG (intermediate interaction potential); and EPLAS, PE, SPH and PC (essentially no interaction potential). The two phospholipids with the least interaction potential for either of the alkaline-earth cations were PC and SPH. Na+ and K+ ion interactions with PA, CL, PI and PG were unique and resulted in positive chemical-shift changes relative to the chemical shifts in the presence of Cs+ ions. Relative to both Cs+ and K+ ions, chemical shifts in the presence of Na+ ions were deshielded delta greater than 0.1 ppm in the order PA greater than CL greater than PI greater than PG.

Binding, Competitive↗

Breast disease evaluation with fat-suppressed magnetic resonance imaging.

Thirty patients with a variety of pathologically confirmed malignant and benign pathologic lesions of the breast were evaluated with a spectrally selective fat suppression imaging technique to obtain fat-suppressed images of the breast. The technique, a selective partial inversion-recovery (SPIR) method, demonstrated the architectural relationship of malignant and benign tumors with respect to the normal water-containing elements of the breast. These relationships included signs of advanced malignant disease such as tissue retraction, invasive growth, and multicentricity, which appeared on the fat-suppressed images. Fat-suppressed imaging provided useful information for assessing the breasts of both pre- and postmenopausal women, especially in the latter group, where fatty involution of the breast is common. Microcysts, which are normally not visualized by conventional methods, were demonstrated and associated with patients having confirmed fibrocystic disease of the breast. As expected, the SPIR technique did not improve the ability to distinguish between tissues having similar T1 and T2 relaxation time values, such as malignant tumors and normal breast parenchymal tissues. The technique was able to demonstrate that the intense lipid signal, known to be responsible for obscuring the borders of water-fat interfaces and small tumors, could be eliminated in a variety of pathological settings.

Breast↗

Phospholipid profiles of human colon cancer using 31P magnetic resonance spectroscopy.

Phospholipids of 16 malignant and 11 non-malignant human colon specimens were analyzed using a chloroform-methanol analytical reagent in conjunction with 31P magnetic resonance spectroscopy (MRS) at 202.4 MHz. Sixteen individual generic phospholipids were identified and quantified for statistical intergroup comparisons. Statistically significant elevations in the relative concentrations of lysophosphatidylcholine and phosphatidylcholine plasmalogen were seen in malignant tissues along with significantly depressed levels of sphingomyelin and phosphatidylethanolamine plasmalogen. The malignant and non-malignant tissue groups were further differentiated by the detection of the minor phospholipids, lysophosphatidylcholine plasmalogen, lysophosphatidylethanolamine plasmalogen, lysophosphatidic acid and phosphatidylglycerol exclusively present in the malignant tissues and by significant changes in computed phospholipid metabolic indices that were dominated by choline containing lipids. The 31P MRS methods used represent an advancement over previous protocols for identifying and quantifying major and minor tissue phospholipids making this the first direct study of membrane phospholipids in human colon tissues using 31P MRS. The phospholipid profiles obtained may provide important information regarding the nature of the malignant cell's membrane system and identify markers which may be used to estimate malignant propensity, aggressiveness of disease and provide prognostic information.

Adenocarcinoma↗

MRI appearance of multiple papilloma of the breast.

Magnetic resonance imaging (MRI) is capable of providing a different diagnostic perspective in the evaluation of breast lesions. Its application in a single patient with multiple papilloma of the breast is described. MRI convincingly demonstrated the multicentric nature of the disease and helped to select a proper treatment plan. This report makes it clear that MRI could serve as an adjunct to mammography and sonography in selected cases.

Breast↗

The effects of age on phosphatic metabolites of the human crystalline lens.

Paired human lenses ranging from 2 to 96 yr old (n = 17) were harvested within 2 hr post-mortem and immersed in liquid nitrogen. Phosphorus containing metabolites from perchloric acid extracts were quantitated using phosphorus-31 nuclear magnetic resonance spectroscopy. Low-energy metabolites detected include the phosphomonoesters (PME) hexose-6 phosphate, alpha-glycerol phosphate, fructose 1,6-diphosphate, beta-glycerol phosphate (beta-GP), uncharacterized phosphomonoesters at 4.63 delta, 4.34 delta and 3.05 delta, phosphorylethanolamine (PE), inosine and adenosine monophosphates, and phosphorylcholine (PC). Inorganic orthophosphate (Pi), glucose 1-phosphate and glycerol 3-phosphorylcholine were the other low-energy metabolites detected. High-energy metabolites phosphocreatine (PCr), adenosine tri- and di-phosphates (ATP, ADP), nucleoside diphosphorylsugars (NS) and the dinucleotides were also detected. The following metabolic indices were calculated: PCr/Pi, PME/Pi; ATP/Pi, PCr/ATP, ATP/ADP, PE + PC, PC/PE, energy charge, phosphorylation potential, and the energy modulus. A significant linear increase with age (P less than 0.05) occurred only in the uncharacterized resonance at 3.05 delta (r = 0.4593). Significant linear decreases with age (P less than 0.05) occurred in the uncharacterized resonance at 4.63 delta (r = -0.5950), beta-GP (r = -0.5018), PCr (r = -0.4495), N.S. (r = -0.4882). There was a significant (P less than 0.05) linear decrease in the energy modulus (ratio of high-energy to low-energy metabolites).

Adolescent↗

31P magnetic resonance phospholipid profiles of neoplastic human breast tissues.

Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the Scheffé comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue.

Breast↗

Clinical magnetic resonance spectroscopy of human breast disease.

Using image-guided volume-selection techniques, in vivo phosphorus-31 magnetic resonance (MR) spectroscopic profiles were obtained from 12 patients with malignant breast tumors, six patients with benign breast tumors, and nine volunteers with no underlying pathologic condition. Phosphatic metabolites identified in the spectral profiles included the phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphorylated glycans (PG), phosphocreatine (PCr) and adenosine triphosphate (ATP). Based on the results of previous high-resolution ex vivo 31P MR spectroscopic analyses of breast tissues, the resonance of PG was identified in malignant and benign breast tumors. Malignant tumors were found to have a significantly (P less than .05) lower concentration of (PME + Pi) than normal breast parenchyma, and were distinguishable from both benign tumors and normal breast parenchymal tissue by significantly (P less than .01) elevated levels of (PDE + PG). 31P MR spectroscopy is the first technique potentially capable of differentiating among malignant breast tumors, benign breast tumors, and normal breast parenchymal tissues based on their in vivo phosphatic metabolic profiles.

Adenosine Triphosphate↗

Human crystalline lens phospholipid analysis with age.

Paired human crystalline lenses (n = 21, patient ages 20-79 years) were extracted for lipids with chloroform-methanol 2:1, using the Folch method. The extracted crude lipids were analyzed at 202.4 MHz by phosphorus-31 magnetic resonance spectroscopy (31P NMR). Fourteen membrane phospholipids were detected including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylcholine plasmalogen (PC plas), phosphatidylethanolamine (PE), phosphatidylethanolamine plasmalogen, lysophosphatidylethanolamine (PA), phosphatidylglycerol (PG), lysophosphatidylglycerol, phosphatidylserine (PS), phosphatidic acid, phosphatidylinositol, sphingomyelin (SPH), and two uncharacterized phospholipids. The uncharacterized phospholipid at 0.13 was the predominant phospholipid, comprising 43.20% of the lens phospholipid profile. A decrease in mole percent of phosphorus concentrations of PE, PC plas, and PC and an increase in SPH correlated with age. The following computed indices decreased with age: PC/PG and PE/PS; PC + PE; (PC + PC plas); and PC/PS. The following computed indices increased with age: (PC + SPH)/(PE + PS), SPH/PG, (PC + SPH)/(PE + PS), LPC/PC, LPE/PE, SPH/PE, and SPH/PC. Changes in membrane phospholipids of the crystalline lens with age as detected by 31P NMR can be used to fingerprint lens maturation.

Adult↗

31P magnetic resonance spectroscopy of human colon cancer.

Phosphatic metabolite profiles of 19 malignant and normal human colon specimens were analyzed by techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy at 202.4 MHz. Thirty-one individual phosphorus-containing intermediates of metabolism were identified and quantified for statistical intergroup comparisons. Elevations in relative concentrations of phosphorylethanolamine, IMP, NADP 2'-P, an uncharacterized resonance at 3.72 delta, glycerol 3-phosphorylcholine, phosphorylated glycans and the nucleoside diphosphosugars were seen in malignant tissues concurrently with reductions in relative concentrations of phosphorylcholine, phosphocreatine (PCr), and ATP. The malignant and normal tissue groups were further characterized and contrasted by computing metabolic indices from spectral data. Significant elevations in phosphomonoesters, glycerolphosphodiesters, the ratio of phosphorylethanolamine/phosphorylcholine, and phosphomonoesters/inorganic orthophosphate were detected in malignant tissues along with significant reductions in the ratios of PCr/inorganic orthophosphate, PCr/ATP, the energy charge of the adenylate system and the tissue energy modulus. These results revealed significant alterations in high energy metabolism, low energy metabolism, and membrane metabolism characteristic of malignant tissues. The reduction in high energy phosphates ATP and PCr was balanced by the net increase in nucleoside diphosphosugar and a shift in equilibrium to metabolism involving low energy phosphomonoesters. The spectral data of the tumors, which were of epithelial origin, demonstrated minor metabolites not previously detected in tissue extract analysis of malignant tissues. Detection of these minor metabolites represents an indirect measurement of phospholipid metabolism in malignant tissues.

Cell Membrane↗

P-31 NMR analysis of phospholipids from cultured human corneal epithelial, fibroblast and endothelial cells.

Corneal epithelial, fibroblast and endothelial cells, cultured from human donors, were analyzed to determine their characteristic phospholipid profiles by 31P NMR. Tissue phospholipid profiles from epithelial, fibroblast and endothelial cell cultures were evaluated to differentiate the individual cell types and to identify resonances that typically appear in high-resolution phospholipid profiles of whole corneas. Phosphatidylcholine, phosphatidylethanolamine plasmalogen, an uncharacterized phospholipid at 0.13 delta, phosphatidylinositol, phosphatidylserine and sphingomyelin were determined to be, in decreasing order of concentration, the major phospholipids detected in these three cultured corneal cell types. Indices of phospholipid metabolism representing total plasmalogen content, total choline-containing lipids and the total choline-containing lipids less those synthesized through the plasmalogen pathway were found to differentiate the three cell types. Minor phospholipids cardiolipin, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine (LPC) and LPC plasmalogen not usually reported in studies of corneal phospholipids using other techniques, were useful in discriminating between cell types. Phospholipid profiles of the whole cornea provide important information concerning the biochemistry and pathology of the tissue, however, phospholipid analysis of individual components of the cornea, such as the epithelial, fibroblast and endothelial cells, makes it possible to understand the contribution of specific cellular constituents to the spectral information obtained from the whole cornea.

Cells, Cultured↗

31P NMR of phospholipid glycerol phosphodiester residues.

Saponification of extracted tissue phospholipids yields a set of isolated glycerol 3-phosphoryl phospholipid polar headgroups from which semi-quantitative 31P NMR spectra can be obtained. The resonance signals from these molecules, which frequently have been reported as uncharacterized phosphate signals observed in perchloric acid extracts of tissue, can be used as an aid in the characterization of isolated phospholipids and of tissue phospholipid 31P NMR profiles. 31P NMR chemical-shift values of the resonances at pH 7 in water and relative to 85% phosphoric acid are: glycerol 3-phosphocholine (-0.13 delta), glycerol 3-phosphoethanolamine (0.42 delta), glycerol 3-phospho(monomethyl)ethanolamine (0.29 delta), glycerol 3-phospho(dimethyl)ethanolamine (0.16 delta), glycerol 3-phosphoserine (0.14 delta), glycerol 3-phosphoinositol (-0.07 delta), glycerol 3-phosphoglycerol (0.92 delta), bis(glycerol 3-phospho)glycerol (0.79 delta), serine ethanolamine phosphodiester (-0.46 delta), glycerol 3-phosphate (0.60 delta; 4.29 delta at pH 10) glycerol 2-phosphate (0.15 delta; 3.92 delta at pH 10). In addition, analysis of extracted cancer tissue phospholipid samples yielded a new and uncharacterized polar headgroup fragment with a chemical-shift value of 0.29 delta that is independent of sample pH.

Animals↗

31P magnetic resonance spectroscopic profiles of neoplastic human breast tissues.

Phosphorus-containing metabolites of human breast tissues from malignant, benign, and noninvolved breast parenchymal specimens were examined by using techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy. Twenty-four separate resonances arising from the established phosphorylated metabolites of high-energy- and low-energy-phosphate intermediary metabolism were identified and quantitated. Subsequent to magnetic resonance spectroscopic analysis, the data from the three tissue groups were compared and contrasted on a statistical basis by using Scheffé simple and complex contrast procedures. Theories of tumor metabolism and biochemical interactions were invoked, including the tissue high-energy-/low-energy-phosphate modulus, the phosphomonoester/Pi ratio, and 10 other metabolic indices. The data demonstrated the ability of 31P magnetic resonance spectroscopy to differentiate among the three tissue groups. Both benign and malignant tumors demonstrated comparable Warburg effects. Phosphomonoester metabolism was shown to be altered in neoplastic tissues relative to the noninvolved tissues. Phosphocreatine was elevated in benign tumors. This elevation in phosphocreatine plus a parallel elevation in an uncharacterized phosphate resonating at a chemical shift of 3.66 delta permits the important differentiation between malignancy and benignancy in human breast disease. The tissue energy modulus indicated that benign tissue is relatively more aerobic than noninvolved tissue and significantly more aerobic than malignant tissue.

Biomarkers, Tumor↗

Intracavitary birdcage resonator: applications to the human prostate.

Twenty-five patients with prostatic cancer were prospectively examined with a prototype endorectal surface coil featuring a birdcage resonator circuit design. The purpose was to determine the safety of an intracavitary probe for magnetic resonance (MR) imaging of the pelvis that incorporates the "inside-out" characteristics of a volume coil design and allows high-resolution MR imaging of the prostate and potentially serves as an alternative to single-loop intracavitary surface coils. Clinically useful images supplementing images obtained with the body or external surface coils were obtained with the prototype probe. It was tolerated by all patients enrolled in the study, and none experienced side effects. The cylindrically symmetric sensitivity profile of the probe allowed identification of prostate tumors and pelvic lymph node and bone metastases. Volume-type coils may improve endopelvic MR imaging when used alone or in combination with external coil systems.

Feasibility Studies↗

Esophageal cancer phospholipid characterization by 31P NMR.

Phospholipid extracts of surgical tissue specimens from 18 patients, consisting of normal esophagus, distal esophageal tumor and normal stomach, were analyzed using 31P NMR. The prominent phospholipids detected in these tissues included cardiolipin (CL), phosphatidylethanolamine plasmalogen, phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylcholine plasmalogen and phosphatidylcholine (PC). Very small quantities of the phospholipids lysophosphatidylcholine, phosphatidic acid, phosphatidylglycerol, and an uncharacterized phospholipid at -0.13 delta also were detected in some of the 54 tissue specimens analyzed. The mean relative concentrations of these phospholipids, in mole percentages of total detected phosphorus, were determined from the acquired spectra and used to differentiate among the three tissue groups. The relative concentrations of the following phospholipids differed significantly (p < 0.001) among the respective tissue groups: normal esophagus vs esophageal tumor, PS, SPH, PI, PC; normal esophagus vs normal stomach, CL, PE, PS, SPH; esophageal tumor vs normal stomach, CL, PE. Membrane phospholipids implicated in modulating the growth and metastases of tumors of epithelial origin can be profiled to discriminate among normal esophagus, distal esophageal tumor and normal stomach using 31P NMR.

Cardiolipins↗

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience.

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.

Adolescent↗