PubMed Health⌕ Search

Biomedical subjects

T R Brown

Publications and source records attributed to T R Brown.

At least 91 records · Page 5Linked to original sources
PubMed1994

A method for calculating the distribution of pH in tissues and a new source of pH error from the 31P-NMR spectrum.

The true distribution of the pH in tissues can be determined from the in vivo 31P-nuclear magnetic resonance (NMR) spectrum by converting the parts per million (PPM) axis of the pH responsive resonance to pH using the Henderson-Hasselbalch equation. In addition, the intensity axis of the resonance must be divided by the derivative of the Henderson-Hasselbalch equation to correct for the nonlinear relationship between pH and PPM. This nonlinear relationship causes the apparent center of the resonance in PPM to be dependent not only on the center of the pH distribution but also on its width and distance from the pKa, where Ka is the association constant. Therefore, the pH determined from uncorrected spectra may be in significant error, particularly if the pH distribution is distant from the pKa and is broad. The method was applied to the isolated perfused Morris hepatoma 5123C to determine the distribution of intracellular pH (pHi) using resonances from two intracellular compounds. The two resonances did not report the same pHi unless the spectral data were properly corrected. The method should be of interest to anyone interested in pHi.

Animals↗
PubMed1994

MR imaging of the patellofemoral compartment.

This article reviews the applications of MR imaging of the patellofemoral compartment. Axial plane images are the most informative for abnormalities of this compartment. The role of MR imaging in the evaluation of the medial synovial plica and in the detection of chondromalacia is discussed. MR imaging can reliably detect and delineate the complex of injuries associated with patellar dislocations and valgus hyperextension.

Cartilage Diseases↗
PubMed1993

Identification of a putative tumor marker in breast and colon cancer.

Application of a recently developed phospholipid saponification procedure to malignant colon or breast tissue produces an unidentified phosphodiester resonance in the 31P nuclear magnetic resonance spectrum which appears to correlate with malignancy. Glycerol phosphodiesters were prepared from a malignant breast tumor by a Folch extraction of the tissue followed by saponification of the resulting phospholipids. These compounds were separated by ion exchange chromatography and the compound responsible for this new resonance was isolated and identified as glycerol 2-phosphoglycerol by high resolution nuclear magnetic resonance spectroscopy. Confirmation of this structure was achieved by chemical synthesis of glycerol 2-phosphoglycerol. Attempts to isolate the phospholipid responsible for this resonance showed that it is not derived from a new class of phospholipids but is most likely an artifact of the new saponification procedure used. Glycerol 2-phosphoglycerol is formed via glycerol 2,3-(cyclic) phosphate derived from phosphatidylcholine followed by reaction with glycerol. Malignant tissue is more prone to produce this compound than is nonmalignant tissue and the differences between these tissue types may be a form of phosphatidylcholine that is present in higher concentrations in malignant tumor membranes than in those of normal tissue.

Biomarkers, Tumor↗
PubMed1993

Experimental design of 31P MRS assessment of human forearm muscle function: restrictions imposed by functional anatomy.

The restrictions imposed by the functional anatomy of the finger flexor muscles on the experimental design of 31P MRS assessment of human forearm muscle function employing surface coil localization and voluntary exercise were investigated. It was found that 31P MRS metabolic data of finger flexor muscle should be correlated with mechanical data of combined flexion of only the ring and little fingers, rather than all four fingers as has been commonly the case in previously reported studies.

Adenosine Triphosphate↗
PubMed1993

Evaluation of chondromalacia of the patellofemoral compartment with axial magnetic resonance imaging.

Axial magnetic resonance (MR) imaging of the patellofemoral compartment was performed in 75 patients with arthroscopic correlation. Proton density and T2(2500/20/80) weighted images were obtained in all patients. Chondromalacia in stages I and II could not be reliably identified with MR imaging. For the evaluation of stage III and IV chondromalacia, the accuracy of MR was 89%. Focal or diffuse areas of increased or decreased signal alterations of the hyaline cartilage without a contour deformity or cartilaginous thinning do not correlate reliably with arthroscopic staging of chondromalacia. A normal signal intensity is no assurance that softening of the cartilage is not present. The most reliable indicators of chondromalacia are focal contour irregularities of the hyaline cartilage and/or thinning of the hyaline cartilage associated with high signal intensity changes within frank defects or contour irregularities with T2-weighted images. The poor MR-arthroscopic correlation in earlier stages of chondromalacia may be due in part to the subjective basis of the arthroscopic diagnosis. In conclusion, stage I and II chondromalacia of the patellofemoral compartment cannot be reliably evaluated with MR imaging. Stage III and IV chondromalacia is reliably evaluated with MR using the combination of proton density and T2-weighted images.

Arthroscopy↗
PubMed1993

Molecular genetics of human androgen insensitivity.

Androgen insensitivity syndromes represent one cause of human male pseudohermaphroditism related to defects in the androgen receptor. The formation of a biologically active androgen receptor complex with testosterone and 5 alpha-dihydrotestosterone is required for normal androgen action during fetal development and differentiation of the internal accessory sex glands and external genitalia. Cloning of the human androgen receptor complementary DNA and genetic screening of human subjects with the clinical and biochemical features of androgen insensitivity using the polymerase chain reaction, denaturing gradient gel electrophoresis and nucleotide sequencing techniques have led to the identification of molecular defects in the androgen receptor. The complexity of phenotypic presentation by affected subjects with the complete or partial forms of androgen insensitivity is represented by the heterogeneity of androgen receptor gene mutations which include deletions and point mutations, with the latter causing inappropriate splicing of RNA, premature termination of transcription and amino acid substitutions. The naturally occurring mutations in the androgen receptor of subjects with androgen insensitivity represent a base upon which we can increase our understanding of the structure and function of the androgen receptor in normal physiology and disease.

Androgens↗
PubMed1993

Triiodothyronine (T3) improves cardiovascular function during hemorrhagic shock.

Prior work showed that an intact thyroid axis augments survival from hemorrhagic shock (HS); this study assesses the effects of specific thyroid-related hormones on cardiovascular (CV) function during HS. Following thyroidectomy, 32 conditioned male dogs were subjected to HS to a mean arterial pressure (MAP) of 60 mm Hg for 90 min then to 40 mm Hg for 30 min. Postshock (PS), the dogs received thyroid-releasing hormone (TRH; 2 mg/kg), thyroid-stimulating hormone [control (TSH; 10 IU)], T3 (12 micrograms/kg), or T4 (40 micrograms/kg). Thirty minutes following treatment (PTX), they were resuscitated with shed blood and 50 ml/kg saline. CV and hormonal parameters were measured PS, PTX, postresuscitation (PR), and on day 2 (D2). There were no PS differences in CV parameters between groups. Following treatment, T3 significantly increased MAP (59.0 +/- 13 vs, 39.9 +/- 2.2 mm Hg) and cardiac output (CO; 0.92 +/- 0.1 vs. 0.80 +/- 0.1 liter/min; P < 0.05 by ANOVA). TRH treatment significantly improved PTX MAP (62.7 +/- 10 vs. 40.8 +/- 2.1; P < 0.05 by ANOVA). TSH and T4 did not significantly change PTX MAP or CO. There were no significant CV differences in the four groups following resuscitation or on D2. In conclusion, T3 improves MAP and CO during hemorrhagic shock. TRH transiently improved PTX blood pressure. Further study of the mechanism of this beneficial response afforded by T3 administration is warranted.

Animals↗
PubMed1993

Severe burns resulting from magnetic resonance imaging with cardiopulmonary monitoring. Risks and relevant safety precautions.

Cardiopulmonary monitoring may be desirable during magnetic resonance imaging (MRI) of hemodynamically unstable patients, but must be performed with great caution. This case report describes a severe burn associated with pulse oximetry use during MRI scanning. Risk of this injury is greatest in infants and in individuals with obtundation, general anesthesia, insensate limbs or impairments of verbal communication. Several safety precautions are described. Preparation and monitoring of patients undergoing MRI scanning with cardiopulmonary monitoring should be performed only by specially trained personnel.

Burns↗
PubMed1992

Androgen receptor gene mutations in human prostate cancer.

We screened human prostate cancer tissues for the presence of somatic mutations in the hormone binding domain of the androgen receptor (AR) gene. Exons E-H were amplified from genomic DNA using the polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE), which separates DNA fragments that differ by only a single base. We detected a mutation in exon E of the hormone binding domain in 1 of 26 specimens of untreated organ-confined stage B prostate cancer. The mutation was not detectable in peripheral blood lymphocyte DNA. Lymphocyte DNA (wild-type AR) migrated in DGGE as a single band. The tumor DNA migrated in DGGE as four bands, consistent with the presence of cells with mutant AR plus cells with wild-type AR and indicating that the tumor contained a somatic mutation. To our knowledge, a somatic AR gene mutation has not been reported previously. Sequencing revealed a G----A substitution in codon 730, changing valine to methionine. Codon 730 is in a region highly conserved among all steroid receptors. The abundance of the mutated fragment (about 50% of the DNA in the specimen) indicates its presence in cells with a growth advantage. A somatic mutation could be detected by DGGE if it represented at least 10% of the sample. Failure to detect mutations in other specimens analyzed may be due to this limit of sensitivity, the presence of mutations in other parts of the AR, or a low frequency of mutations in early stage disease.

Amino Acid Sequence↗
PubMed1992

Fructose metabolism in the human erythrocyte. Phosphorylation to fructose 3-phosphate.

In human erythrocytes, the first step in the metabolism of fructose is generally thought to be phosphorylation to fructose 6-phosphate catalysed by hexokinase. In variance with this assumption, we show here that fructose in these cells is metabolized primarily to fructose 3-phosphate by a specific 3-phosphokinase. This process has an overall estimated Km of 30 mM with respect to extracellular fructose and an apparent Vmax. of 0.6 mumol/h per ml. At a fixed concentration of fructose in the medium, the accumulation of fructose 3-phosphate was linearly dependent on the duration of incubation up to 5 h and was not affected by glucose. Once accumulated, fructose 3-phosphate appears to be degraded and/or relatively slowly metabolized, decreasing by only approximately 30% after a 12 h incubation in a fructose-free medium.

Erythrocytes↗
PubMed1992

Detection of significant features and statistical analysis of 2D and 3D images of 31P metabolites.

The application of spectroscopy techniques to the study of normal and pathological tissue is currently limited by the difficulties of acquiring precisely localized spectra and analyzing the resulting, relatively low signal-to-noise data. Interpretation of multivoxel spectroscopy data is greatly facilitated by estimating peak parameters and representing their spatial distribution as metabolite images. We present here the new algorithm MIMSTATS, which performs an analysis of these images and determines whether the variations in the images are statistically significant. The algorithm has been developed and tested by application to 31P CSI data from the human forearm and brain. Our results demonstrate that MIMSTATS can detect signal at a very low signal-to-noise ratio in a reliable and reproducible fashion and provides a sound basis for testing hypotheses concerning differences in distribution of metabolites.

Algorithms↗
PubMed1992

Marek's disease virus-transformed chicken T-cell lines respond to lymphokines.

Current assays for chicken interleukin-2 (IL-2) utilize mitogen-activated lymphocytes. However, very high inter-assay variability and sporadic high background proliferation limit their usefulness. In view of the above, several Marek's disease virus (MDV)-transformed T-cell lines (which grow well in a serum-supplemented medium) were tested for a response to chicken IL-2 when grown in serum-free media. Five of six lines examined showed a dose-dependent proliferative response to chicken T-cell conditioned media. One line, MDCC-CU14, was chosen for further studies. In addition to the tumor cells' dose-dependent responses to semi-purified chicken IL-2, they expressed T-cell activation antigens on the cell surface. Furthermore, the level of surface expression was enhanced on cells provided IL-2. Co-incubation of the tumor cells with monoclonal antibody INN-CH-16 (specific for an antigen on the surface of activated T-cells) and IL-2 resulted in a modulation of lymphokine-induced proliferation. Together, these data suggest that signalling mechanisms in MDV T-cell tumors are intact and that these lines can be used as an assay for chicken T-cell lymphokines. Furthermore, they provide an interesting model for the study of avian and mammalian T-cell transformation. Implications for the study of Marek's disease are also discussed.

Animals↗
PubMed1992

Menisci of the knee: radial MR imaging correlated with arthroscopy in 259 patients.

Similar to arthrograms, radial plane magnetic resonance (MR) images of the knee provide cross-sectional images of the menisci that are perpendicular to the long axis of the meniscus. The authors evaluated 259 consecutive patients who underwent MR imaging of the knee and arthroscopy. Radial multiplanar gradient-recalled-echo imaging was performed--with repetition time of 700 msec, echo times of 12 and 31 msec (700/12, 31), and a flip angle of 20 degrees--as well as sagittal spin-echo imaging (2,500/20, 80). The radial and sagittal images were interpreted separately and then in combination, and findings were compared with arthroscopic reports. There was no statistical difference between the interpretations of the radial and sagittal images in the evaluation of the menisci. When the interpretations of the radial and sagittal images were combined, the sensitivity and specificity improved slightly. The radial images increased the conspicuity of meniscal tears but at the expense of anatomic detail. The sagittal images enabled better evaluation of the meniscocapsular attachment region and some flap tears of the meniscal free edge. The interpretive accuracies of the combination of sagittal and radial images were 92% and 93% for the medial and lateral menisci, respectively.

Adult↗
PubMed1992

Proceedings of a National Cancer Institute workshop: MR spectroscopy and tumor cell biology.

In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed.

Humans↗
PubMed1992

Two-dimensional 31P-chemical shift imaging of intramuscular heterogeneity in exercising human forearm muscle.

Two-dimensional phosphorus chemical shift imaging (2D-31P-CSI) was used to investigate macroscopic heterogeneity within the flexor digitorum profundus (FDP) muscle of the human forearm during exercise. Subjects performed low-frequency steady-state finger flexion exercise at submaximal work levels using a bulb ergometer. The number of fingers actively involved in finger flexion exercise was varied in a total of 12 experiments. Active muscles could be determined by the increase of Pi and decrease of phosphocreatine observed in the localized spectra. Within the FDP, regions of active and inactive fibers were significantly different in levels of Pi and phosphocreatine (P less than 0.01) during flexion of individual fingers. Individual flexion of the index finger was found to involve only fibers in the deep region of the FDP. Fibers in the central region were found to be involved in flexion of the middle finger, and fibers in the superficial region were involved in flexion of the ring and little fingers. The results of this study demonstrate the potential of 2D-31P-CSI for in vivo investigation of intramuscular heterogeneity in human skeletal muscle.

Adult↗
PubMed1992

Regulation of oxygen consumption in fast- and slow-twitch muscle.

Phosphorus nuclear magnetic resonance spectra and steady-state O2 consumption rates were obtained from ex vivo arterially perfused cat biceps brachii (fast twitch) and soleus (slow twitch) muscles during and after periods of isometric twitch stimulation at 30 degrees C. In the biceps muscles, steady-state O2 consumption increased and phosphocreatine (PCr) concentration decreased progressively with stimulation. PCr recovery after these stimulation periods followed first-order kinetics with a half time of 10 min. The results in the biceps could be explained by a feedback control of cellular respiration by ADP concentration. In the soleus, steady-state O2 consumption also increased and PCr concentration decreased as stimulation rates increased. The half time for PCr recovery in the soleus was approximately 5 min, but, in contrast to the pattern in the biceps, the kinetics was not first order. There was an overshoot during the recovery period in the PCr content of soleus and a corresponding undershoot of Pi compared with resting values. Mitochondrial regulation by ADP is not sufficient to account for respiratory control in slow-twitch soleus. The respiration rate in neither muscle was dependent on the Pi content. Thus we conclude that the mechanism of control of cellular respiration is both quantitatively and qualitatively different in fast- and slow-twitch skeletal muscle.

Adenosine Diphosphate↗