PubMed Health⌕ Search

Biomedical subjects

T R Brown

Publications and source records attributed to T R Brown.

At least 73 records · Page 4Linked to original sources
PubMed1995

Diagnosis of popliteus injuries with MR imaging.

OBJECTIVE: Popliteal muscle and tendon injuries are thought to be unusual. This report describes the magnetic resonance (MR) appearances of popliteus muscle and tendon injuries. DESIGN AND PATIENTS: The study included 24 patients where the diagnoses of popliteal injuries were prospectively made based on MR appearances. The study group was taken from 2412 consecutive knee MRIs. The injuries were characterized as to involving the muscular or tendinous portions of the popliteus apparatus. RESULTS: In 95.8% (23/24) of patients, the tears of the popliteus involved the muscular portion. The injuries were either partial and interstitial or complete. Three patients had tears of both the muscular and tendinous portions or the tendon alone. The anterior and posterior cruciate ligaments were torn in 16.7% (4/24) and 29.2% (7/24) of patients, respectively. There were medial and lateral meniscal tears in 45.8% (11/24) and 25% (6/24) of patients, respectively. There were injuries of the medial and lateral collateral ligaments in 8.3% (2/24) and 4.2% (1/24) of patients, respectively. Bone bruises and/or fractures were seen in 33.3% (8/24) patients. In 8.3% (2/24) of patients, the popliteus injury was an isolated finding. CONCLUSION: Popliteus muscle and tendon injuries are not uncommon. They usually occur in conjunction with other significant injuries of the knee and can be characterized with MR imaging.

Adolescent↗
PubMed1995

Identification of galactitol 2-phosphate and galactitol 3-phosphate in the lens of galactose-fed rats.

Production of unusual phosphorylated metabolites in the lens is one of several changes caused by hyperglycemia. Sorbitol 3-phosphate (Sor-3P) and fructose 3-phosphate (Fru-3P) are two such compounds identified in the diabetic lens, and galactitol 2-phosphate (Gal-2P) and galactitol 3-phosphate (Gal-3P) are identified here in the galactosemic lens. These new compounds are the first example of galactitol metabolism in mammalian tissue other than liver. Sor-3P and Fru-3P are also present in the galactosemic lens, apparently synthesized directly from their precursors, sorbitol and fructose, which are elevated in the lens due to increased flux of glucose through the aldose reductase (AR) pathway. The NADPH necessary to support this increased flux is derived from activation of the hexose monophosphate shunt (HMPS), which is clearly demonstrated by a large increase in the concentration of sedoheptulose 7-phosphate (Sed-7P), a HMPS-specific metabolite. Additionally, during 3 weeks of galactose feeding, there is a dramatic increase in lenticular concentrations of galactitol, sorbitol, galactose, and fructose and a sharp decrease in inositol. Glucose remains unchanged. A precipitous loss of both phosphorylated and nonphosphorylated metabolites occurs after 3 weeks, possibly due to lens rupture.

Animals↗
PubMed1995

Signalling by the p60c-src family of protein-tyrosine kinases.

The c-src gene family has nine known members (blk, c-fgr, fyn, hck, lck, lyn, c-src, c-yes and yrk), each encoding a cytoplasmic protein-tyrosine kinase (PTK) believed to be involved in signal transduction. The c-src PTKs contain three domains (SH1, SH2 and SH3) that are found in many other signalling proteins. The SH1 domain has PTK activity, whilst the SH2 and SH3 domains are involved in mediating protein-protein interactions by binding to phosphotyrosine-containing and proline-rich motifs, respectively. The expression patterns of the c-src PTKs suggest that they function in a broad range of biological situations, in many cases regulating the behaviour of terminally-differentiated, post-mitotic cell types. Targeted disruption of members of the c-src family in transgenic mice has confirmed important roles for p56lck and p59fym(T) in T-lymphocyte maturation and activation, but has also revealed unexpected roles for p60c-src in bone maintenance and for p59fym(B) in learning and memory. There is increasingly detailed information about the biochemical nature of the signalling pathways in which the c-src PTKs operate and about the other signalling proteins with which they interact. The c-src PTKs can associate with activated receptor PTKs, including the receptors for platelet-derived growth factor and epidermal growth factor, by means of SH2-phosphotyrosine binding. The c-src PTKs also associated with transmembrane proteins that lack PTK activity, frequently by means of interactions involving their unique amino-terminal sequences.

Animals↗
PubMed1995

Characterization of alternative amino acid substitutions at arginine 830 of the androgen receptor that cause complete androgen insensitivity in three families.

We have studied two different missense mutations at arginine-830 in exon 7 of the human androgen receptor (hAR) gene that cause complete androgen insensitivity (CAIS) in three families. These substitutions result from point mutations at nucleotide 2489: a G-->T transversion causes Arg830Leu and a G-->A transition causes Arg830Gln. Genital skin fibroblasts of the patients have negligible androgen-binding capacity. The mutations were recreated in an hAR cDNA expression vector that was transiently transfected into COS-1 cells. Both mutant androgen receptors have increased dissociation rate constants and apparent equilibrium rate constants when measured with 5 alpha-dihydrotestosterone or the synthetic, nonmetabolizable androgens, mibolerone or methyltrienolone. The mutant androgen-binding activities share a distinctive thermal misbehavior. At 37 degrees C R830Q and R830L are about 40% and 10% of normal, respectively. At 22 degrees C both mutants gain androgen binding while the normal decreases by 20%; for R830Q the augmented value approaches 60% of the normal. During prolonged 18 h incubation at 37 degrees C, androgen binding of the normal AR is stable while that of both mutants decreases by at least 85%. Both mutants have a very reduced ability to transactivate a cotransfected androgen-responsive reporter gene, but R830Q is better than R830L. We conclude that arginine-830 is important for A-R complex stability, and that its replacement by glutamine or leucine yields distinctive functional aberrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Quasi-linear relationship between Gibbs free energy of ATP hydrolysis and power output in human forearm muscle.

The postulated strictly linear descriptions of the rate dependence of oxidative phosphorylation in skeletal muscle on the free energy of ATP hydrolysis (delta GP) over the range of physiological steady states fail to harmonize with reported findings of identical basal respiration rates in mammalian muscles at different delta GP values. The relevance of an extension of the strictly linear description to a description deriving from enzyme kinetics that predicts a sigmoidal dependence was investigated in human finger flexor muscle using 31P-nuclear magnetic resonance spectroscopy. At constant pH 7.0, the experimental variation of adenine nucleotide concentrations with power output, which reflects the rate of oxidative phosphorylation, was compared with predictions by various formulations of adenine nucleotide control of respiration. The quasi-linear sigmoidal description was found to be statistically equivalent but physiologically superior to the strictly linear description. The predicted maximal oxidatively sustained steady-state power output and rate-dependent sensitivity of respiration to changes in delta GP were in agreement both with theoretical considerations and with experimental observations in the present study and other studies of intact mammalian skeletal muscle.

Adenosine Diphosphate↗
PubMed1995

Lobe-specific apoptotic cell death in rat prostate after androgen ablation by castration.

It is well established that androgens are central to regulation of the growth of the mammalian prostate gland. Conversely, androgen deprivation by castration induces rapid cell death in the ventral prostate via an apoptotic mechanism. To date, most studies of cell death in the rodent prostate have focused on the ventral lobe, with little attention directed to the dorsal and lateral lobes. The results presented herein demonstrate that cell death in the rat prostate gland caused by castration is lobe specific. In particular, castration caused decreases in wet weights and protein contents of all three prostatic lobes, but these events were more rapid and profound in the ventral than in the dorsal and lateral lobes. Reduced epithelial cell size was apparent in the three lobes as well. However, castration resulted in loss of DNA content in the ventral lobe only. To confirm this finding, and to examine apoptosis of individual cells, we used in situ labeling of fragmented DNA, supported by biochemical analysis of DNA integrity in agarose gels. With both approaches, significant cell death in response to castration was seen in the ventral lobe but not the dorsal and lateral lobes. Taken together, these results clearly indicate that there are lobe-specific differences in the response of the rat prostate to androgen ablation by castration, with apoptotic cell death occurring in the ventral lobe of the prostate but to a far lesser extent, if at all, in the dorsal and lateral lobes. Moreover, castration caused apoptotic death of both epithelial and stromal cells of the ventral prostate, with these cells dying throughout the ductal network of the ventral prostate rather than being restricted to a particular region. We suggest that lobe-specific differences in androgen responsiveness in the rat prostate may provide an appropriate model for the study of androgen-independent prostatic cell survival during tumor progression.

Animals↗
PubMed1995

Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chickens.

The present study examines the role of thyroid cell injury in the initiation of autoimmune thyroiditis by iodine in Obese strain (OS) chickens, a strain genetically susceptible to spontaneous autoimmune thyroiditis. OS and normal strain chickens were placed on an iodine depletion regimen started in ovo. This regimen is known to prevent thyroiditis in OS chickens. The chickens were injected with NaI every 24 h for up to 7 days starting at 3 weeks of age. Both strains showed evidence of mild thyrocyte injury 12 h after NaI. However, significant and sustained infiltration, beginning 24 h after NaI, was seen only in the OS. The infiltrating cells were primarily mononuclear. Polymorphonuclear cells were not observed. Immunohistological analysis showed the infiltrate to be composed of CD8 T cells, CD4 T cells, B cells, and macrophages in the ratio 40:20:22:17. The infiltration was sustained and progressive for at least 7 days. Thyroid infiltration after NaI repletion was significantly reduced in OS chickens tolerized to thyroglobulin at hatching. Prior treatment with the antioxidant drug ethoxyquin completely prevented both the thyrocyte injury and the infiltration induced by iodine. Treatment with antioxidant drugs had no effect on the uptake and incorporation of iodine by the thyroid. In summary, 1) iodine caused thyrocyte injury in both OS and normal chickens. 2) The injury was followed by cellular infiltration in the OS but not in normal chickens. 3) The infiltration appeared to be immune mediated in being primarily lymphocytic and at least partially thyroglobulin sensitive. 4) Prevention of thyroid injury by antioxidant drug treatment also prevented infiltration. We conclude that thyroid cell injury may be an initial event in the induction of autoimmune thyroiditis by iodine.

Animals↗
PubMed1995

31P-nuclear magnetic resonance evidence of an activated hexose-monophosphate shunt in hyperglycemic rat lenses in vivo.

Using 31P-nuclear magnetic resonance spectroscopy, we have identified elevated concentrations of sedoheptulose-7-phosphate (S-7-P) in lenses from three animal models of hyperglycemia: streptozotocin-induced diabetic rats, galactose-fed rats, and xylose-fed rats. This observation provides a unique and independent confirmation of the activation of the hexose monophosphate shunt (HMPS) pathway in the hyperglycemic lens in vivo. While the elevation in concentration of S-7-P was very dramatic, the other HMPS metabolites in these tissues were below the threshold of detection, as expected for the HMPS pathway near equilibrium. In terms of nonenzymatic glycation, these results suggest that the only HMPS metabolite of importance in the hyperglycemic rat lens is S-7-P. Although in the diabetic lens its role appears to be relatively minor, in the galactosemic lens this compound may be an important contributor to the increased production of advanced glycosylation end products.

Animals↗
PubMed1995

Production of fructose and fructose-3-phosphate in maturing rat lenses.

PURPOSE: A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. METHODS: Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31P-NMR for sugar phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. RESULTS: Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites--sorbitol, fructose, sorbitol-3-phosphate, and fructose-3-phosphate--was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. CONCLUSION: Aging lenses accumulate increased concentrations of fructose and fructose-3-phosphate. Because fructose-3-phosphate is a potent glycating agent and a potential in vivo source of 3-deoxyglucosone, its accumulation in the lens, along with fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses.

Aging↗
PubMed1995

Richter hernia: a rare complication of laparoscopy.

A case of Richter hernia in the umbilical trocar site following laparoscopic cholecystectomy is presented. The fascia was not specifically closed after the laparoscopic cholecystectomy. The Richter hernia presented 2 days later, suffered a delay in diagnosis because of persistence of bowel function and required bowel resection 9 days later. A total of four known postoperative umbilical trocar site hernias, two of which were Richter hernias, have been reported following 1,979 laparoscopic cholecystectomies in two large community hospitals in Colorado: Saint Joseph Hospital in Denver and North Colorado Medical Center in Greeley. Thus, periumbilical trocar site incisional hernias following laparoscopic cholecystectomy are rare but potentially dangerous because of the susceptibility to Richter hernia.

Cholecystectomy, Laparoscopic↗
PubMed1994

Dual interleaved 1H and proton-decoupled-31P in vivo chemical shift imaging of human brain.

A technique is demonstrated to obtain interleaved proton (1H) and 1H-decoupled phosphorus (31P) spectra of human brain using 2D CSI. A modified commercial full-body imager and a dual-tuned birdcage head-coil were employed. Because proton relaxation times are shorter than those of phosphorus, TR(1H) can be chosen to be shorter than TR(31P), thus permitting a 1H acquisition to be inserted in each 31P cycle. The scheme results in significant time savings as both CSI data sets are obtained concurrently with patient loading, coil tuning, shimming, and imaging needed to be done only once.

Adult↗
PubMed1994

Characterization of a phosphonium analog of choline as a probe in 31P NMR studies of phospholipid metabolism.

Tumors and transformed cells have been shown by 31P NMR to contain elevated concentrations of two phosphomonoesters, phosphorylcholine and phosphorylethanolamine, involved in phospholipid metabolism. In order to understand the biochemical basis for these phenomena new methods are needed to allow for analysis of the relevant metabolic pathways in intact cells. One such promising tool may be phosphonium-choline, a 31P NMR-visible analog of choline in which the trimethyl-ammonium group of choline has been replaced with a trimethyl-phosphonium moiety. As shown previously [Sim et al. Biochem. J. 154, 303 (1976)], this compound is non-toxic and readily metabolized by cultured cells into phospholipids. In this paper we describe in greater detail some of the chemical and NMR spectroscopic properties of this material. Most significantly we show here that the chemical shift of phosphonium-choline is sensitive to the phosphorylation state of the analog and that the phosphonium nucleus is NMR-visible even after its incorporation into phospholipid. The unique properties of this analog should make it possible to use high-field 31P NMR to follow the flux of phosphonium-choline through the Kennedy pathway in intact perfused cells cultures.

Animals↗
PubMed1994

Investigation of broad resonances in 31P NMR spectra of the human brain in vivo.

Broad resonances that lie underneath the familiar small molecule profile of in vivo 31P NMR spectra can make accurate spectral integration of these mobile phosphates difficult. The two major broad components are the phosphate contained in the hydroxyapatite in cranial bone and the phosphodiester moiety in partially mobile membrane phospholipids. They can be removed with post-acquisition processing but this results in distortion of lineshapes and intensities and interferes with accurate quantitation. We have employed an off-resonance saturation procedure to eliminate the bone resonance and isolate the signal from the membrane phospholipids by subtraction. Selective saturation of the phospholipid resonance increases the clarity of the sharp peaks downfield from the phosphocreatine peak. Selective saturation 3-D chemical shift imaging techniques were used to create a localized phospholipid profile of the entire brain simultaneously. Monitoring localized phospholipid concentration may be important in studying demyelinating diseases.

Bone and Bones↗
PubMed1994

Two configurations of the four-ring birdcage coil for 1H imaging and 1H-decoupled 31P spectroscopy of the human head.

The four-ring birdcage resonator, a new class of dual-tuned birdcage resonators, is described. We report two configurations of the coil: the low-pass, high-pass (LP-HP) and the low-pass, low-pass (LP-LP), both of which can be operated in dual quadrature mode at 1.5 T. As head coils, both configurations exhibit greatly reduced tuning interactions between frequencies, permitting rapid, noniterative tuning. Compared with single-tuned, two-ring birdcage resonators of similar volume, the sensitivity and transmitter efficiencies of the resonators are better than 85% for the proton frequency and the same to within 5% for the phosphorus frequency. Circuit models have been developed to refine coil tuning and aid the calculation of B1 field contour plots. Both configurations have been used for integrated examinations involving acquisition of high-quality 1H images and 1H-decoupled 31P CSI spectra of the human head. A scaled-down version of the LP-LP configuration has been demonstrated for use with the human calf.

Head↗
PubMed1994

Simultaneous and interleaved multinuclear chemical-shift imaging, a method for concurrent, localized spectroscopy.

A method is proposed for carrying out chemical-shift imaging simultaneously on several nuclei (1H and 31P in this example), using a commercial clinical NMR imager fitted with a second RF channel and a dual-tuned birdcage coil to fit the human head. Nuclei of different gamma are examined at the same field of view by exciting each nucleus successively at times proportional to gamma during the same phase-encoding gradient waveform. Thus, each higher-gamma nucleus is exposed to a smaller area of the gradient. Additionally, since in vivo protons typically have a shorter T1 and roughly an order of magnitude higher sensitivity than phosphorus, it is possible to interleave 1H-only acquisitions between the simultaneous 1H, 31P observations while the lower-gamma nucleus relaxes. Consequently, additional information is obtained with either higher spatial resolution or greater sensitivity (more signal averaging) without lengthening the duration of the examination.

Computer Simulation↗
PubMed1994

Age- and lobe-specific responses of the brown Norway rat prostate to androgen.

We examined the effects of age and of increasing concentrations of testosterone on the wet weight, protein content, cell number, and cell size of the ventral, dorsal, and lateral lobes of the Brown Norway rat prostate. Young (3 mo of age) and aged (15, 17, and 21 mo of age) rats received implants of increasing sizes of testosterone-filled Silastic capsules for 3 mo. Wet weights of the prostate were the same in untreated young (6-mo-old) and aged (18-24-mo-old) rats. Testosterone administration resulted in serum testosterone concentrations ranging from physiologic to superphysiologic. Dose-dependent increases in wet weights and protein contents were seen in the ventral, dorsal, and lateral prostatic lobes of both young and aged rats. For each given dose of testosterone, including doses that resulted in serum testosterone concentrations within the physiologic range, the weights and protein contents of the dorsal and lateral lobes were greater in old (24-mo-old) than in young (6-mo-old) rats, indicating an effect of age in these lobes. In contrast, ventral prostate weights and protein contents increased equivalently in young and aged rats with increasing testosterone concentration. DNA content, a measure of cell number, increased significantly in the dorsal and lateral lobes as a function of testosterone dose and age, but in the ventral lobe did not differ with testosterone dose or age. Quantitative morphologic analyses showed significant hypertrophy of epithelial cells throughout each of the three lobes in both young and aged rats treated with testosterone. Taken together, these results indicate that the prostate of Brown Norway rats shows age and lobe-specific responses to androgen with respect to wet weight, protein content, cell number, and cell morphology.

Aging↗