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1.
Folia Morphol (Warsz) ; 82(1): 190-193, 2023.
Article in English | MEDLINE | ID: mdl-34845718

ABSTRACT

Variations of the nerves of the forearm can lead to unexpected clinical findings during physical examination. Additionally, surgery in this region might encounter and potentially damage the nerve in such patients. Here, we present a case of a high split of the median nerve and discuss the findings of the case as well as review salient reports in the literature. Knowledge of such a variation can be important in patient diagnosis and treatment.


Subject(s)
Forearm , Median Nerve , Humans
2.
Integr Org Biol ; 4(1): obac013, 2022.
Article in English | MEDLINE | ID: mdl-35814192

ABSTRACT

Synopsis: Archerfishes (Toxotidae) are variously found in the fresh- and brackish-water environments of Asia Pacific and are well known for their ability to shoot water at terrestrial prey. These shots of water are intended to strike their prey and cause it to fall into the water for capture and consumption. While this behavior is well known, there are competing hypotheses (blowpipe vs. pressure tank hypothesis) of how archerfishes shoot and which oral structures are involved. Current understanding of archerfish shooting structures is largely based on two species, Toxotes chatareus and T. jaculatrix. We do not know if all archerfishes possess the same oral structures to shoot water, if anatomical variation is present within these oral structures, or how these features have evolved. Additionally, there is little information on the evolution of the Toxotidae as a whole, with all previous systematic works focusing on the interrelationships of the family. We first investigate the limits of archerfish species using new and previously published genetic data. Our analyses highlight that the current taxonomy of archerfishes does not conform to the relationships we recover. Toxotes mekongensis and T. siamensis are placed in the synonymy of T. chatareus, Toxotes carpentariensis is recognized as a species and removed from the synonymy of T. chatareus, and the genus Protoxotes is recognized for T. lorentzi based on the results of our analyses. We then take an integrative approach, using a combined analysis of discrete hard- and soft-tissue morphological characters with genetic data, to construct a phylogeny of the Toxotidae. Using the resulting phylogenetic hypothesis, we then characterize the evolutionary history and anatomical variation within the archerfishes. We discuss variation in the oral structures and the evolution of the mechanism with respect to the interrelationships of archerfishes, and find that the oral structures of archerfishes support the blowpipe hypothesis but soft-tissue oral structures may also play a role in shooting. Finally, by comparing the morphology of archerfishes to their sister group, we find that the Leptobramidae has relevant shooting features in the oral cavity, suggesting that some components of the archerfish shooting mechanism are examples of co-opted or exapted traits. Sinopsis Malay: Pelbagai jenis Ikan Sumpit (Toxotidae) dapat dijumpai di persekitaran air tawar dan payau di Asia Pasifik dan mereka terkenal dengan kebolehan mereka menembak air ke arah mangsa di darat. Tembakan air ini bertujuan untuk menyerang mangsa mereka dan menyebabkan mereka jatuh ke dalam air untuk ditangkap dan dimakan. Walaupun tingkah laku ini diketahui umum, terdapat hipotesis yang bersaing (hipotesis sumpitan vs. tangki tekanan) tentang cara ikan sumpit menembak dan struktur mulut yang terlibat. Pemahaman semasa tentang struktur menembak ikan sumpit adalah sebahagian besarnya berdasarkan dua spesies, Toxotes chatareus dan T. jaculatrix. Kami tidak pasti sama ada semua ikan sumpit mempunyai struktur mulut yang sama untuk menembak air, jika variasi anatomi terdapat dalam struktur mulut ini, atau bagaimana ciri-ciri ini telah berkembang. Tambahan pula, terdapat sedikit maklumat tentang evolusi Toxotidae secara keseluruhan, dengan semua penyelidikan sistematik sebelum ini memfokuskan pada hubungan saling keluarga. Kami pada mulanya mengkaji had spesies ikan sumpit ini menggunakan data genetik baharu dan yang diterbitkan sebelum ini. Analisis kami menunjukkan bahawa taksonomi semasa ikan sumpit tidak mematuhi hubungan yang kami perolehi. Toxotes mekongensis dan T. siamensis diletakkan bersama kesinoniman T. chatareus, Toxotes carpentariensis yang diiktiraf sebagai satu spesies dan dikeluarkan daripada kesinoniman T. chatareus, dan genus Protoxotes yang diiktiraf untuk T. lorentzi adalah berdasarkan hasil analisis kami. Kemudian kami mengambil pendekatan integratif, menggunakan analisis gabungan karakter morfologi tisu keras dan lembut diskret dengan data genetik, untuk membina filogeni Toxotidae. Menggunakan hipotesis filogenetik yang terhasil, kami kemudian mencirikan sejarah evolusi dan variasi anatomi dalam ikan sumpit. Kami membincangkan variasi dalam struktur mulut dan evolusi mekanisme berkenaan yang berkaitan dengan ikan sumpit, dan mendapati bahawa struktur mulut ikan sumpit menyokong hipotesis sumpitan tetapi struktur mulut tisu lembut juga mungkin memainkan peranan dalam cara menembak. Akhir sekali, dengan membandingkan morfologi ikan sumpit kepada kumpulan saudara mereka, kami mendapati bahawa Leptobramidae mempunyai ciri penangkapan yang relevan dalam rongga mulut mereka, menunjukkan bahawa beberapa komponen mekanisme penangkapan ikan sumpit merupakan contoh ciri-ciri yang diikut-sertakan atau diguna semula.

3.
Proc Biol Sci ; 281(1783): 20140321, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24695431

ABSTRACT

Living reef fishes are one of the most diverse vertebrate assemblages on Earth. Despite its prominence and ecological importance, the origins and assembly of the reef fish fauna is poorly described. A patchy fossil record suggests that the major colonization of reef habitats must have occurred in the Late Cretaceous and early Palaeogene, with the earliest known modern fossil coral reef fish assemblage dated to 50 Ma. Using a phylogenetic approach, we analysed the early evolutionary dynamics of modern reef fishes. We find that reef lineages successively colonized reef habitats throughout the Late Cretaceous and early Palaeogene. Two waves of invasion were accompanied by increasing morphological convergence: one in the Late Cretaceous from 90 to 72 Ma and the other immediately following the end-Cretaceous mass extinction. The surge in reef invasions after the Cretaceous-Palaeogene boundary continued for 10 Myr, after which the pace of transitions to reef habitats slowed. Combined, these patterns match a classic niche-filling scenario: early transitions to reefs were made rapidly by morphologically distinct lineages and were followed by a decrease in the rate of invasions and eventual saturation of morphospace. Major alterations in reef composition, distribution and abundance, along with shifts in climate and oceanic currents, occurred during the Late Cretaceous and early Palaeogene interval. A causal mechanism between these changes and concurrent episodes of reef invasion remains obscure, but what is clear is that the broad framework of the modern reef fish fauna was in place within 10 Myr of the end-Cretaceous extinction.


Subject(s)
Biodiversity , Biological Evolution , Coral Reefs , Fishes/physiology , Animals , Extinction, Biological , Phylogeny
4.
J Appl Clin Med Phys ; 14(2): 4051, 2013 Mar 04.
Article in English | MEDLINE | ID: mdl-23470934

ABSTRACT

We analyzed a large patient and volunteer study of external respiratory motion in order to develop a population database of respiratory information. We analyzed 120 lung, liver, and abdominal patients and 25 volunteers without lung disease to determine the extent of motion using the Varian Real-Time Position Management system. The volunteer respiratory motion was measured for both abdominal and thoracic placement of the RPM box. Evaluation of a subset of 55 patients demonstrates inter- and intrafraction variation over treatment. We also calculated baseline drift and duty cycle for patients and volunteers. The mean peak-to-peak amplitude (SD) for the patients was 1.0 (0.5) cm, and for the volunteers it was abdomen 0.8 (0.3) cm and thoracic 0.2 (0.2) cm. The mean period (SD) was 3.6 (1.0) s, 4.2 (1.1)s, and 4.1 (0.8) s, and the mean end exhale position (SD) was 60% (6), 58% (7), and 56% (7) for patient, volunteer abdomen, and volunteer thoracic, respectively. Baseline drift was greater than 0.5 cm for 40% of patients. We found statistically significant differences between the patient and volunteer groups. Peak-to-peak amplitude was significantly larger for patients than the volunteer abdominal measurement and the volunteer abdominal measurement is significantly larger than the volunteer thoracic measurement. The patient group also exhibited significantly larger baseline drift than the volunteer group. We also found that peak-to-peak amplitude was the most variable parameter for both intra- and interfraction motion. This database compilation can be used as a resource for expected motion when using external surrogates in radiotherapy applications.


Subject(s)
Lung Neoplasms/physiopathology , Lung Neoplasms/radiotherapy , Movement , Respiratory Mechanics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Middle Aged , Motion , Reproducibility of Results , Sensitivity and Specificity , Young Adult
5.
J Appl Clin Med Phys ; 13(4): 3810, 2012 Jul 05.
Article in English | MEDLINE | ID: mdl-22766951

ABSTRACT

Changing pulse repetition frequency or dose rate used for IMRT treatments can alter the number of monitor units (MUs) and the time required to deliver a plan. This work was done to develop a practical picture of the magnitude of these changes. We used Varian's Eclipse Treatment Planning System to calculate the number of MUs and beam-on times for a total of 40 different treatment plans across an array of common IMRT sites including prostate/pelvis, prostate bed, head and neck, and central nervous system cancers using dose rates of 300, 400 and 600 MU/min. In general, we observed a 4%-7% increase in the number of MUs delivered and a 10-40 second decrease in the beam-on time for each 100 MU/min of dose rate increase. The increase in the number of MUs resulted in a reduction of the "beam-on time saved". The exact magnitude of the changes depended on treatment site and planning target volume. These changes can lead to minor, but not negligible, concerns with respect to radiation protection and treatment planning. Although the number of MUs increased more rapidly for more complex treatment plans, the absolute beam-on time savings was greater for these plans because of the higher total number of MUs required to deliver them. We estimate that increasing the IMRT dose rate from 300 to 600 MU/min has the potential to add up to two treatment slots per day for each IMRT linear accelerator. These results will be of value to anyone considering general changes to IMRT dose rates within their clinic.


Subject(s)
Radiotherapy, Intensity-Modulated/methods , Head and Neck Neoplasms/radiotherapy , Humans , Male , Particle Accelerators , Pelvis/diagnostic imaging , Prostate/diagnostic imaging , Radiation Protection , Radiography , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods
6.
Med Phys ; 39(7Part2): 4626, 2012 Jul.
Article in English | MEDLINE | ID: mdl-28516527

ABSTRACT

Respiratory motion complicates radiotherapy treatment of thoracic and abdominal tumours. Simplified respiratory motions such as sinusoidal and single patient traces are often used to determine the impact of motion on respiratory management techniques in radiotherapy. Such simplifications only accurately model a small portion of patients, as most patients exhibit variability and irregularity beyond these models. We have preformed a comprehensive analysis of respiratory motion and developed a software tool that allows for explicit inclusion of variability. We utilize our realistic respiratory generator to customize respiratory traces to test the robustness of the estimate of internal gross target volumes (IGTV) by 4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT for regular breathing motion. When amplitude variability was introduced the accuracy of the estimate slightly, but the absolute differences were still < 3 mm for both modalities. Poor agreement was shown with the addition of baseline drifts. Both modalities were found to underestimate the IGTV by as much as 30% for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate accuracy. The respiratory trace generator was advantageous for examining the difference between 4DCT and CBCT IGTV estimation under variable motions. It provided useful implementation abilities to test specific attributes of respiratory motion and detected issues that were not seen with the regular motion studies. This is just one example of how the respiratory trace generator can be utilized to test applications of respiratory management techniques.

7.
Phys Med Biol ; 55(24): 7439-52, 2010 Dec 21.
Article in English | MEDLINE | ID: mdl-21098915

ABSTRACT

Stereotactic body radiotherapy of lung cancer often makes use of a static cone-beam CT (CBCT) image to localize a tumor that moves during the respiratory cycle. In this work, we developed an algorithm to estimate the average and complete trajectory of an implanted fiducial marker from the raw CBCT projection data. After labeling the CBCT projection images based on the breathing phase of the fiducial marker, the average trajectory was determined by backprojecting the fiducial position from images of similar phase. To approximate the complete trajectory, a 3D fiducial position is estimated from its position in each CBCT project image as the point on the source-image ray closest to the average position at the same phase. The algorithm was tested with computer simulations as well as phantom experiments using a gold seed implanted in a programmable phantom capable of variable motion. Simulation testing was done on 120 realistic breathing patterns, half of which contained hysteresis. The average trajectory was reconstructed with an average root mean square (rms) error of less than 0.1 mm in all three directions, and a maximum error of 0.5 mm. The complete trajectory reconstruction had a mean rms error of less than 0.2 mm, with a maximum error of 4.07 mm. The phantom study was conducted using five different respiratory patterns with the amplitudes of 1.3 and 2.6 cm programmed into the motion phantom. These complete trajectories were reconstructed with an average rms error of 0.4 mm. There is motion information present in the raw CBCT dataset that can be exploited with the use of an implanted fiducial marker to sub-millimeter accuracy. This algorithm could ultimately supply the internal motion of a lung tumor at the treatment unit from the same dataset currently used for patient setup.


Subject(s)
Cone-Beam Computed Tomography/methods , Fiducial Markers , Movement , Radiotherapy/standards , Respiration , Dose Fractionation, Radiation , Humans , Image Processing, Computer-Assisted , Motion , Reproducibility of Results
8.
Article in English | MEDLINE | ID: mdl-19038575

ABSTRACT

The corrections to conventional Franck-Condon factors required by the assumption that an electronic transition takes place in a non-zero time t(0) are investigated using a theory based on the sudden approximation. An explicit expression using a harmonic oscillator model is given for the vibrational progression k'<--0'', where k', 0'' are the vibrational quantum numbers in the final and initial states respectively. The calculations for this case suggest that the effects of a non-zero t(0) will be very small for most molecular electronic spectra, but for certain long progressions the corrections become more significant and may in favourable cases be detectable, thus giving an experimental basis for the concept of a non-zero t(0) and an estimate of its size. Possible examples in the spectra of diatomic molecules where this effect may be found are discussed.


Subject(s)
Models, Chemical , Spectrum Analysis , Vibration
9.
J Dairy Sci ; 88(11): 4120-31, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16230716

ABSTRACT

Radiofrequency (RF) power was investigated as a new, physical (nonchemical), thermal process to disinfect wastewater from dairy and animal facilities. Samples (n = 38) from 8 dairy, 2 calf, and 3 swine facilities in California were collected over a 3-yr period and characterized for their dielectric properties, chemical composition, and suitability for thermal processing using RF power. To establish efficacy for disinfection, selected samples were inoculated with high levels (10(6) to 10(9) cfu/mL) of bacterial pathogens such as Salmonella sp., Escherichia coli O157:H7, and Mycobacterium avium ssp. paratuberculosis and processed with an RF prototype system. The capabilities of RF power as a method for thermal disinfection of wastewater were demonstrated when bacteria pathogens were completely and rapidly (<1 min) inactivated when temperatures of 60 to 65 degrees C were achieved. Furthermore, RF technology can be used for large-scale, batch or continuous and portable applications, allowing significant improvements in energy-use efficiencies compared with conventional thermal (surface heating) technologies. Therefore, RF power has potential as an alternative to disinfect dairy/animal farm wastewater before recycling.


Subject(s)
Agriculture/methods , Dairying/methods , Disinfection/methods , Radio Waves , Water Microbiology , Animals , Cattle , Chemical Phenomena , Chemistry, Physical , Disinfection/economics , Disinfection/instrumentation , Escherichia coli O157 , Hot Temperature , Industrial Waste , Mycobacterium avium subsp. paratuberculosis , Salmonella , Swine , Water/chemistry
10.
Article in English | MEDLINE | ID: mdl-12667186

ABSTRACT

TaqMan real time PCR was used to study the transcriptional activity of the bovine IL-2, IL-6, IL-12p40, IFN-gamma, TNF-alpha and granulocyte-monocyte colony stimulating factor of whole milk cells in bovine mammary gland experimentally infected with Staphylococcus aureus. Cytokine transcriptional activity was monitored at 7, 24 and 32 h Post-infection (Pi). IL-12 and TNF-alpha levels were significantly elevated at 24 h Pi followed by sharp decrease at 32 h pi. IL-2 level was decreased at 32 h pi. IL-12 and IFN-gamma showed a significant interaction at 24 h pi. The significant elevations of the IL-12 and TNF-alpha transcriptional level most likely indicate their important role in regulation of the immune responses of bovine mammary gland in S. aureus infection. Depression of IL-2 could reflect the suppressive nature of the S. aureus mastitis.


Subject(s)
Cytokines/immunology , Mastitis, Bovine/immunology , Milk/immunology , Staphylococcal Infections/immunology , Animals , Cattle , Cytokines/genetics , DNA Primers , Female , Granulocyte-Macrophage Colony-Stimulating Factor , Interferon-gamma , Interleukin-12 , Interleukin-12 Subunit p40 , Interleukin-2 , Interleukin-6 , Milk/cytology , Polymerase Chain Reaction/veterinary , Protein Subunits , RNA, Messenger/analysis , Staphylococcus aureus , Tumor Necrosis Factor-alpha
11.
Lett Appl Microbiol ; 36(5): 293-6, 2003.
Article in English | MEDLINE | ID: mdl-12680941

ABSTRACT

AIMS: To evaluate a spiral plating and microscopic colony counting technique to hasten the quantitation of Mycobacterium paratuberculosis. METHODS AND RESULTS: Broth and milk cultures of M. paratuberculosis were spirally plated onto Middlebrook agar plates and microscopically counted at 8 and 14 days of incubation. The same plates were recounted at 27-28 days of incubation when grossly visible colonies were present. The results were statistically compared with no difference in CFU ml-1 derived from the shorter vs longer incubation times. Other mycobacteria isolates were also plated and microscopically examined and found to be easily distinguishable from M. paratuberculosis. CONCLUSIONS: Microscopic quantitation of spirally plated M. paratuberculosis cultures can be achieved within 8-14 days of plate incubation and compare favourably to counts derived after prolonged incubations. SIGNIFICANCE AND IMPACT OF THE STUDY: The technique could greatly hasten the quantitation of viable M. paratuberculosis.


Subject(s)
Colony Count, Microbial/methods , Mycobacterium avium subsp. paratuberculosis/isolation & purification , Culture Media , Research Design , Time Factors
12.
Med Image Anal ; 6(3): 301-12, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12270234

ABSTRACT

We have designed a prototype three-dimensional ultrasound guidance (3D USB) apparatus to improve the breast biopsy procedure. Features from stereotactic mammography and free-hand US-guided biopsy have been combined with 3D US imaging. This breast biopsy apparatus accurately guides a needle into position for the sampling of target tissue. We have evaluated this apparatus in three stages. First, by testing the placement accuracy of a needle in a tissue mimicking phantom. Second, with tissue mimicking phantoms that had embedded lesions for biopsy. Finally, by comparison to free-hand US-guided biopsy, using chicken breast phantoms. The first two stages of evaluation quantified the mechanical biases in the 3D USB apparatus. Compensating for these, a 96% success rate in targeting 3.2 mm "lesions" in chicken breast phantoms was achieved when using the 3D USB apparatus. The expert radiologists performing biopsies with free-hand US guidance achieved a 94.5% success rate. This has proven an equivalence between our apparatus, operated by non-experts, and free-hand biopsy performed by expert radiologists, for 3.2 mm lesions in vitro, with a 95% confidence.


Subject(s)
Biopsy, Needle/instrumentation , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Computer Graphics , Imaging, Three-Dimensional/instrumentation , Stereotaxic Techniques/instrumentation , Ultrasonography, Mammary/instrumentation , Animals , Biopsy, Needle/methods , Chickens , Equipment Design , Equipment Failure Analysis , Feasibility Studies , Imaging, Three-Dimensional/methods , In Vitro Techniques , Models, Statistical , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity , Ultrasonography, Mammary/methods
13.
Biochem Biophys Res Commun ; 289(4): 869-75, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11735127

ABSTRACT

Prostaglandin endoperoxide H synthases (PGHSs)-1 and -2 have a cyclooxygenase (COX) activity involved in forming prostaglandin G2 (PGG2) from arachidonic acid and an associated peroxidase (POX) activity that reduces PGG2 to PGH2. Suicide inactivation processes are observed for both POX and COX reactions. Here we report COX reaction conditions for PGHS-1 under which complete COX inactivation occurs but with > or = 60% retention of POX activity. The rates of POX inactivation were compared for native oPGHS-1 versus Y385F oPGHS-1, a mutant that cannot form the Tyr385 radical of COX Intermediate II; the rates were the same for both native and Y385F oPGHS-1. Our data indicate that a COX Intermediate II/acyl or product complex is the precursor in COX inactivation. However, another species, probably an Intermediate II-like species but with a radical centered on a tyrosine other than Tyr385, is the immediate precursor for POX inactivation.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Peroxidases/antagonists & inhibitors , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Fatty Acids/chemistry , Fatty Acids/pharmacology , Free Radicals , In Vitro Techniques , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Kinetics , Mutagenesis, Site-Directed , Peroxidases/chemistry , Peroxidases/genetics , Prostaglandin-Endoperoxide Synthases/chemistry , Prostaglandin-Endoperoxide Synthases/genetics , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Sheep , Tyrosine/chemistry
15.
Otol Neurotol ; 22(5): 644-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11568673

ABSTRACT

OBJECTIVE: To discuss the various symptoms and causes of objective tinnitus in children. STUDY DESIGN: Retrospective case review. PATIENTS: Five children who had audible signals emanating from their ears caused by audible spontaneous otoacoustic emissions, palatal myoclonus, arteriovenous malformation, and acoustic trauma. MAIN OUTCOME MEASURE: The tinnitus reported by the patients was linked to acoustic signals that could be measured objectively or heard by the examiner. RESULTS: Four of the five children had essentially normal hearing. The one child who demonstrated a hearing loss audiometrically was thought to have normal hearing sensitivity, but his intense roaring objective tinnitus appeared to mask his low-frequency thresholds. All five patients had measurable acoustic signals in the ear canal that matched the patients' descriptions of their tinnitus. CONCLUSION: The cases illustrate how the objective tinnitus was diagnosed and measured, how a treatment algorithm was applied, and the expected results of treatment. In addition, the cases provide support for the use of psychologic counseling throughout the examination and treatment of objective tinnitus in children.


Subject(s)
Tinnitus/diagnosis , Adolescent , Algorithms , Audiometry, Pure-Tone , Auditory Threshold/physiology , Child , Female , Humans , Male , Otoacoustic Emissions, Spontaneous/physiology , Retrospective Studies , Severity of Illness Index , Tinnitus/physiopathology
17.
Ultrasound Med Biol ; 27(8): 1025-34, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11527588

ABSTRACT

A new core needle breast biopsy system guided by 3-D ultrasound (US) is proposed. Our device provides rapid imaging and real-time guidance, as well as breast stabilization and a needle guidance apparatus using 3-D imaging. The targeting accuracy of our device was tested by inserting a 14-gauge biopsy needle into agar phantoms under 3-D US guidance. A total of 18 0.8-mm stainless-steel beads embedded in the phantoms defined each of the four target positions tested. Positioning accuracy was calculated by comparing needle tip position to the preinsertion bead position, as measured by three observers three times each on 3-D US. The interobserver standard error of measurement was no more than 0.14 mm for the beads and 0.27 mm for the needle tips. A 3-D principal component analysis was performed to obtain the population distribution of needle tip position relative to the target beads for the four target positions. The 3-D 95% confidence intervals were found to have total widths ranging from 0.43 to 1.71 mm, depending on direction and bead position.


Subject(s)
Biopsy, Needle/methods , Breast/pathology , Imaging, Three-Dimensional , Ultrasonography, Mammary , Female , Humans , Observer Variation , Phantoms, Imaging
18.
J Biol Chem ; 276(40): 37547-55, 2001 Oct 05.
Article in English | MEDLINE | ID: mdl-11477109

ABSTRACT

Prostaglandin endoperoxide H synthases-1 and -2 (PGHSs) can oxygenate 18-22 carbon polyunsaturated fatty acids, albeit with varying efficiencies. Here we report the crystal structures of eicosapentaenoic acid (EPA, 20:5 n-3) and linoleic acid (LA, 18:2 n-6) bound in the cyclooxygenase active site of Co(3+) protoporphyrin IX-reconstituted ovine PGHS-1 (Co(3+)-oPGHS-1) and compare the effects of active site substitutions on the rates of oxygenation of EPA, LA, and arachidonic acid (AA). Both EPA and LA bind in the active site with orientations similar to those seen previously with AA and dihomo-gamma-linolenic acid (DHLA). For EPA, the presence of an additional double bond (C-17/C-18) causes this substrate to bind in a "strained" conformation in which C-13 is misaligned with respect to Tyr-385, the residue that abstracts hydrogen from substrate fatty acids. Presumably, this misalignment is responsible for the low rate of EPA oxygenation. For LA, the carboxyl half binds in a more extended configuration than AA, which results in positioning C-11 next to Tyr-385. Val-349 and Ser-530, recently identified as important determinants for efficient oxygenation of DHLA by PGHS-1, play similar roles in the oxygenation of EPA and LA. Approximately 750- and 175-fold reductions in the oxygenation efficiency of EPA and LA were observed with V349A oPGHS-1, compared with a 2-fold change for AA. Val-349 contacts C-2 and C-3 of EPA and C-4 of LA orienting the carboxyl halves of these substrates so that the omega-ends are aligned properly for hydrogen abstraction. An S530T substitution decreases the V(max)/K(m) of EPA and LA by 375- and 140-fold. Ser-530 makes six contacts with EPA and four with LA involving C-8 through C-16; these interactions influence the alignment of the substrate for hydrogen abstraction. Interestingly, replacement of Phe-205 increases the volume of the cyclooxygenase site allowing EPA to be oxygenated more efficiently than with native oPGHS-1.


Subject(s)
Eicosapentaenoic Acid/metabolism , Isoenzymes/metabolism , Linoleic Acid/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Arachidonic Acid/chemistry , Arachidonic Acid/metabolism , Binding Sites , Computer Simulation , Crystallography, X-Ray , Cyclooxygenase 1 , Eicosapentaenoic Acid/chemistry , Isoenzymes/chemistry , Leucine/metabolism , Linoleic Acid/chemistry , Models, Molecular , Mutation , Oxidation-Reduction , Phenylalanine/metabolism , Prostaglandin-Endoperoxide Synthases/chemistry , Protein Conformation , Serine/metabolism , Substrate Specificity , Valine/metabolism
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