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1.
Zhonghua Nei Ke Za Zhi ; 56(5): 353-357, 2017 May 01.
Article in Chinese | MEDLINE | ID: mdl-28460506

ABSTRACT

Objective: Obesity is one of the risk factors for gout. The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI. Methods: A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI. The clinical information was collected and relevant biochemical indices were detected. SPSS software was applied for the statistical analyses. Results: There were significant differences in the ratios of gender, regular exercise, hypertension, tophus, renal insufficiency, hyperlipidemia, impaired glucose metabolism, liver dysfunction among the three groups (all P<0.01). The onset age in overweight [45(36, 55) years] and obese subjects [40(31, 50) years] were earlier than that of the normal weight subjects [50(38, 61) years]. Moreover, waist circumstances [103(99, 108) cm and 94 (90, 98) cm vs 87 (82, 91) cm], systolic pressure [130 (120, 145) mmHg (1 mmHg=0.133 kPa)and 130(120, 140)mmHg vs 128(115, 140) mmHg], diastolic pressure [90 (80, 100) mmHg and 85 (80, 92) mmHg vs 80 (79, 90) mmHg], fasting blood glucose [5.77 (5.30, 6.44) mmol/L and 5.65 (5.19, 6.26) mmol/L vs 5.55 (5.10, 6.15) mmol/L], TG [2.10 (1.46, 3.04) mmol/L and 1.88 (1.35, 2.78) mmol/L vs 1.52 (1.07, 2.39) mmol/L], TC [5.20 (4.55, 5.93) mmol/L and 5.07 (4.46, 5.75) mmol/L vs 4.95 (4.27, 5.65) mmol/L], serum uric acid [483(418, 552) µmol/L and 461(395, 524) µmol/L vs 440 (368, 517) µmol/L], ALT [30 (21, 46) U/L and 25 (18, 36) U/L vs 21 (14, 29) U/L], AST [21(17, 28) U/L and 20 (17, 26) U/L vs 20 (6, 25) U/L], the number of joints involved [2(1, 3)joints and 2(1, 2) joints vs 1(1, 2) joints] in the overweight and obese groups were higher than those in the normal weight group ( all P<0.01). There were no statistical differences in family history, involvement of upper limb joints, kidney stones and coronary heart disease among the three groups (all P>0.05). Conclusions: Obesity is associated with an earlier age of gout onset.With the increase of BMI, the blood pressures, glucose, lipid, serum uric acid, liver transaminase levels and the number of involved joints increased gradually. Cautions should be taken in treating patients with different BMI.


Subject(s)
Gout , Hypertension/blood , Lipids/blood , Obesity , Uric Acid/blood , Blood Pressure , Body Mass Index , Female , Humans , Male , Overweight , Risk Factors
2.
J Am Coll Radiol ; 11(4): 359-61, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24485760

ABSTRACT

The open-microphone sessions at the AMCLC provide a forum for the ACR's membership to be heard. The topics in 2013 included a review of the annual radiology workforce survey, the impact of teleradiology services, and the rationale for the new Imaging 3.0 initiative. Comments from members at the 2013 AMCLC unequivocally illustrated a single overarching theme: anxiety-anxiety about the future of our practices and anxiety about our profession. In light of recent and anticipated changes in health care, radiologists, radiation oncologists, interventional radiologists, nuclear medicine physicians, and medical physicists-members of the ACR-must continue to establish a leadership role in the health care system and serve as a cornerstone for all patient-care delivery models. ACR commissions, networks, institutes, and initiatives will position us for smoother transitions in the persistently altering health care landscape and will ensure that we have the expertise and tools to serve as leaders in health care systems and advocates for our patients in current and future health care systems.


Subject(s)
Delivery of Health Care/trends , Diagnostic Imaging/trends , Entrepreneurship/trends , Forecasting , Health Care Reform/trends , Ownership/trends , Radiology/trends , United States
4.
Curr Probl Diagn Radiol ; 28(2): 29-62, 1999.
Article in English | MEDLINE | ID: mdl-10088064

ABSTRACT

The purpose of this article is to review the MRI characteristics of musculoskeletal tumors, including skeletal and soft tissue masses. MRI has become the premier imaging modality for the evaluation of musculoskeletal tumors because of its excellent soft tissue contrast, its sensitivity to bone marrow and soft tissue edema, and its multiple imaging planes. In a substantial subset of cases, MRI can provide a diagnosis or a short differential diagnosis, while certain tumors have no distinguishing signal characteristics. MRI of musculoskeletal tumors can also be challenging, because the MRI appearance of certain lesions can be misleading, and a knowledge of the instances in which MRI over- and underestimates the malignancy of lesions is invaluable. The importance of correct protocols for tumor evaluation, both in diagnosis and in pre-operative evaluation, are discussed. Common pitfalls that may over- or underestimate the aggresivity of lesions will be highlighted, as will the role of gadolinium enhancement in the evaluation of lesions. The MRI appearance of common benign and malignant muculoskeletal lesions will be illustrated.


Subject(s)
Bone Neoplasms/diagnosis , Magnetic Resonance Imaging , Muscle Neoplasms/diagnosis , Soft Tissue Neoplasms/diagnosis , Adult , Age Distribution , Child , Clinical Protocols , Diagnosis, Differential , Gadolinium , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results
5.
Genet Med ; 1(5): 187-93, 1999.
Article in English | MEDLINE | ID: mdl-11256671

ABSTRACT

PURPOSE: Due to the characteristics of complex traits, many traits may not be amenable to traditional epidemiologic methods. We illustrate an approach that defines an isolated population as the "unit" for carrying out studies of complex disease. We provide an example using the Pima Indians, a relatively isolated population, in which the incidence and prevalence of Type 2 diabetes, gallbladder disease, and rheumatoid arthritis (RA) are significantly increased compared with the general U.S. population. A previous study of RA in the Pima utilizing traditional methods failed to detect a genetic effect on the occurrence of the disease. METHODS: Our approach involved constructing a genealogy for this population and using a genealogic index to investigate familial aggregation. We developed an algorithm to identify biological relationships among 88 RA cases versus 4,000 subsamples of age-matched individuals from the same population. Kinship coefficients were calculated for all possible pairs of RA cases, and similarly for the subsamples. RESULTS: The sum of the kinship coefficient among all combination of RA pairs, 5.92, was significantly higher than the average of the 4,000 subsamples, 1.99 (p < 0.001), and was elevated over that of the subsamples to the level of second cousin, supporting a genetic effect in the familial aggregation. The mean inbreeding coefficient for the Pima was 0.00009, similar to that reported for other populations; none of the RA cases were inbred. CONCLUSIONS: The Pima genealogy can be anticipated to provide valuable information for the genetic study of diseases other than RA. Defining an isolated population as the "unit" in which to assess familial aggregation may be advantageous, especially if there are a limited number of cases in the study population.


Subject(s)
Arthritis, Rheumatoid/genetics , Genealogy and Heraldry , Indians, North American/genetics , Arizona/epidemiology , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/ethnology , Consanguinity , Demography , Family , Female , Genetic Linkage , HLA Antigens/analysis , Humans , Male , Middle Aged
6.
Chem Phys Lipids ; 103(1-2): 1-10, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10701075

ABSTRACT

The ultrasonic absorption, alpha lambda, as a function of temperature and frequency was determined in large unilamellar vesicles (LUVs) in which specific phospholipid side chains were deuterated. Deuteration significantly altered the temperature and frequency dependence of alpha lambda. The frequency change was especially marked, with decreased frequency and broadening of the ultrasound relaxation, even with only minor changes in the phase transition temperature. Deuteration decreased the Tm and enthalpy of the lipid phase transition, as shown by differential scanning calorimetry, whereas electron spin resonance showed that at and above the lipid phase transition, no differences in the mobility as a function of temperature were observed. These results show that the observed increase in ultrasonic absorption in LUVs at the phospholipid phase transition arises from the interaction of ultrasound with the hydrophobic side chains, probably coupling with structural reorganization of small domains of molecules, a process which is maximized at the phase transition temperature.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Liposomes/chemistry , Phosphatidylglycerols/chemistry , Calorimetry, Differential Scanning , Deuterium , Electron Spin Resonance Spectroscopy , Thermodynamics , Ultrasonics
7.
Arthritis Rheum ; 41(8): 1464-9, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9704646

ABSTRACT

OBJECTIVE: To describe the clinical features and familial distribution of rheumatoid arthritis (RA) in the Pima Indians. METHODS: From 1965 through 1990, all cases of RA as defined by the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 criteria or all cases of seropositive, erosive disease as defined by the Rome criteria were identified in individuals who were age 20 years and older and were of 50% or more Pima/Tohono-O'odham heritage. Radiographs were reviewed by 2 musculoskeletal radiologists who were blinded to case status. Kinship coefficients were used to evaluate familial aggregation. RESULTS: Eighty-eight RA cases were identified from this population-based sample. Over 66% of the cases had seropositive disease, over 60% had erosive disease, and over 40% had subcutaneous nodules. Of the 88 RA cases, 40 were members of families with more than 1 RA case. The remainder were simplex cases. CONCLUSION: In this population, clinical markers of severe RA were present in a majority of cases. The presence of familial aggregation for RA in the Pima Indians suggests underlying genetic factors in disease pathogenesis.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/genetics , Indians, North American/genetics , Indians, North American/statistics & numerical data , Adult , Aged , Arthritis, Rheumatoid/diagnosis , Hand/diagnostic imaging , Humans , Middle Aged , Observer Variation , Pedigree , Prevalence , Radiography , Serologic Tests
8.
J Digit Imaging ; 11(3): 116-20, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9718501

ABSTRACT

In the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention, radiographs of the hands and knees were taken of participants 60 years and older as part of the study of arthritis and musculoskeletal conditions. The purpose of the study was to decide the digitizing resolution to be used for these radiographs. A set of wrist and hand radiographs (N = 49) was graded by two radiologists for degree of bone erosions and served as a "gold standard." The radiographs were then digitized at three resolution levels; low-resolution 150 microns (2001 x 1634 x 12 bit matrix); intermediate-resolution 100 microns (3000 x 2400 x 12 bit matrix); and high-resolution 50 microns (4900 x 3000 x 12 bit matrix). A comparison of the digital images versus the gold standard reading was made at the three resolutions by two radiologists. Kappa statistics suggested fair (K > .4) to excellent (K > .75) agreement between the gold standard and the images at all levels. Intraclass correlation coefficient suggested high agreement between readers (ICC > .5), with minimal individual reader effect. Variance component estimates showed that the major contribution (78-83%) to scoring came from variability in the images themselves, not from the readers. The 100 microns resolution was selected over the 150 and 50 microns on the basis of practical considerations such as storage requirements, display time, and easier manipulation of the digital images by the readers.


Subject(s)
Hand/diagnostic imaging , Radiographic Image Enhancement/methods , Wrist Joint/diagnostic imaging , Arizona/epidemiology , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/ethnology , Humans , Indians, North American , Middle Aged , Nutrition Surveys , Osteoarthritis/diagnostic imaging , Osteoarthritis/ethnology , United States/epidemiology
10.
Radiology ; 202(3): 739-44, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9051028

ABSTRACT

PURPOSE: To assess the diagnostic potential of the rim-to-center differential enhancement ratio in the magnetic resonance (MR) imaging differentiation of benign from malignant musculoskeletal masses. MATERIALS AND METHODS: Dynamic gadolinium-enhanced fast multiplanar spoiled gradient-recalled acquisition in the steady state imaging was performed to evaluate 17 one and soft-tissue masses (10 malignant, seven benign) in 14 patients. The rim-to-center differential enhancement ratio was determined from images at the maximal enhancement rate. The difference in differential enhancement ratios between benign and malignant masses was evaluated and compared with the maximum rate of enhancement for each mass. RESULTS: Nine of 10 malignant masses showed rapid rim enhancement with delayed central fill-in. This enhancement pattern was absent in benign masses. The average rim-to-center differential enhancement ratio was 0.64 +/- 0.26 for malignant masses and -0.16 +/- 0.33 for benign masses (P < .001). This difference was statistically significant. The average maximum rate of enhancement was 3.41%/sec +/- 2.20 for malignant masses and 2.74%/sec +/- 2.46 for benign masses (P > .05). CONCLUSION: Intratumoral enhancement patterns of malignant and benign masses differ because of differences in vascular architecture. These preliminary results suggest that the rim-to-center differential enhancement ratio has potential as an additional parameter for the MR imaging differentiation of indeterminate musculoskeletal masses.


Subject(s)
Bone Neoplasms/diagnosis , Magnetic Resonance Imaging , Muscle Neoplasms/diagnosis , Adolescent , Adult , Aged , Contrast Media , Diagnosis, Differential , Drug Combinations , Female , Gadolinium , Gadolinium DTPA , Humans , Male , Meglumine , Middle Aged , Organometallic Compounds , Pentetic Acid/analogs & derivatives
11.
Crit Rev Diagn Imaging ; 38(6): 535-68, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9442978

ABSTRACT

While the plain film and nuclear medicine bone scan are still the traditional imaging modalities used in the evaluation of musculoskeletal infection, the cross-sectional imaging modalities, computed tomography (CT) and magnetic resonance imaging (MRI), have become critical in the delineation of many types of musculoskeletal infection. In particular, the evaluation of soft tissue infections, including cellulitus, myositis, fasciitis, abscess, and septic arthritis are often best evaluated by MRI or CT due to their excellent anatomic resolution and soft tissue contrast. Even in osseous infection, CT and MRI can give better anatomic delineation of the extent of infection. In cases where the plain film and nuclear medicine bone scan findings are complicated due to previous surgery, trauma, or underlying illness, the anatomic resolution and soft tissue contrast provided by MRI and CT are often necessary to determine if underlying infection exists. MRI's visualization of the bone marrow allows for the sensitive detection of osteomyelitis, although specificity for the diagnosis of osteomyelitis is aided by other findings, including cortical destruction. The CT and MRI findings in the spectrum of musculoskeletal infections are discussed and contrasted, and pitfalls in their evaluation of musculoskeletal infection are described.


Subject(s)
Bacterial Infections/diagnosis , Bone Diseases/microbiology , Magnetic Resonance Imaging , Muscular Diseases/microbiology , Tomography, X-Ray Computed , Abscess/diagnosis , Abscess/diagnostic imaging , Arthritis, Infectious/diagnosis , Arthritis, Infectious/diagnostic imaging , Bacterial Infections/diagnostic imaging , Bone Diseases/diagnosis , Bone Diseases/diagnostic imaging , Bone Marrow/pathology , Bone and Bones/injuries , Bone and Bones/surgery , Cellulitis/diagnosis , Cellulitis/diagnostic imaging , Cellulitis/microbiology , Evaluation Studies as Topic , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/diagnostic imaging , Humans , Muscle, Skeletal/injuries , Muscle, Skeletal/surgery , Muscular Diseases/diagnosis , Muscular Diseases/diagnostic imaging , Myositis/diagnosis , Myositis/diagnostic imaging , Myositis/microbiology , Osteomyelitis/diagnosis , Osteomyelitis/diagnostic imaging , Sensitivity and Specificity , Soft Tissue Infections/diagnosis , Soft Tissue Infections/diagnostic imaging
12.
Orthop Clin North Am ; 27(3): 559-74, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8649737

ABSTRACT

Benign bone-forming tumors are common in children. Careful radiographic imaging is necessary to plan surgical treatment. Careful histologic study is necessary to distinguish osteoblastoma from more aggressive tumors. Osteoid osteoma should be considered when the child or adolescent presents with pain in an extremity or along the spine.


Subject(s)
Bone Neoplasms/diagnosis , Osteoblastoma/diagnosis , Osteoma, Osteoid/diagnosis , Adolescent , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Child , Humans , Osteoblastoma/pathology , Osteoblastoma/therapy , Osteoma, Osteoid/pathology , Osteoma, Osteoid/therapy
14.
Radiographics ; 15(2): 349-66, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7761640

ABSTRACT

Magnetic resonance (MR) imaging is the most sensitive and accurate imaging technique for evaluation of musculoskeletal tumors. With increasing clinical experience, however, an overlap between the classic characteristics of benign and malignant tumors is frequently observed. In a prospective analysis of 87 consecutive cases of musculoskeletal tumors, the malignancy of skeletal lesions was correctly assessed with MR imaging in 55% of the cases. In 39% of the cases, the malignancy of skeletal lesions was overestimated with MR imaging. Correlation with plain radiography is extremely important in such cases and would have resulted in correct assessment of 73% of the skeletal lesions. For soft-tissue lesions, a large variability is found in the benign versus malignant appearances of lesions on MR images, with poor correlation between classic benign characteristics and the benignity of the lesion (17% of cases). The exceptions are hemangiomas and lipomas, which have characteristic appearances on MR images. Knowledge of potentially misleading appearances of musculoskeletal tumors on MR images allows more accurate diagnosis of such tumors.


Subject(s)
Bone Neoplasms/diagnosis , Magnetic Resonance Imaging , Muscular Diseases/diagnosis , Soft Tissue Neoplasms/diagnosis , Adolescent , Adult , Bone Diseases/diagnosis , Bone Neoplasms/diagnostic imaging , Child , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prospective Studies , Radiography
15.
Radiology ; 191(3): 747-9, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8184056

ABSTRACT

Plain radiographs and computed tomographic scans obtained in a severely neutropenic patient with acute lymphoblastic leukemia and cytomegalovirus-associated enterocolitis revealed a pattern of prolonged mucosal adherence of oral contrast agent to the small bowel. This pattern was seen as long as 16 weeks after administration of contrast agent and has been seen previously only in patients who have received bone marrow transplants. Two sets of intestinal biopsy specimens contained crystals that coated denuded mucosa at the site of ulceration and later were trapped within the lamina propria. Electron diffraction and energy-dispersive radiographic analysis showed that these crystals were composed of barium sulfate.


Subject(s)
Barium Sulfate , Intestinal Mucosa/diagnostic imaging , Administration, Oral , Barium Sulfate/administration & dosage , Biopsy , Crystallization , Cytomegalovirus Infections/complications , Enterocolitis/complications , Enterocolitis/diagnostic imaging , Enterocolitis/pathology , Humans , Intestinal Mucosa/pathology , Intestines/diagnostic imaging , Intestines/pathology , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Radiography , Tissue Adhesions
16.
Radiology ; 187(2): 465-7, 1993 May.
Article in English | MEDLINE | ID: mdl-8475291

ABSTRACT

The radiographic findings in two children with acute "recall" pneumonitis, associated with administration of Adriamycin (doxorubicin hydrochloride) and actinomycin D at variable intervals after local radiation therapy, were presented to emphasize the unique radiographic appearance and clinical course. A 10-year-old girl underwent radiation therapy 9 weeks after completing an initial cycle of chemotherapy. Within hours of the resumption of chemotherapy, she was in clinical respiratory distress. Chest radiography showed a well-defined area of alveolar consolidation in the periphery of the right lung corresponding to the area of radiation. Shortness of breath and right chest rales developed in a 15-year-old boy within 12 hours of the resumption of chemotherapy 6 weeks after radiation therapy was completed. Chest radiography showed an alveolar infiltrate extending from the apex to the base of the right lung corresponding to the area of radiation. Symptoms may be confused with an infectious pathogenesis; thus, knowledge of the history of radiation therapy and the radiation port is important in initiating treatment with steroids rather than antibiotics.


Subject(s)
Doxorubicin/adverse effects , Pneumonia/etiology , Radiation Injuries/diagnostic imaging , Acute Disease , Adolescent , Child , Dactinomycin/adverse effects , Female , Humans , Lung/diagnostic imaging , Lung/radiation effects , Male , Pneumonia/chemically induced , Pneumonia/diagnostic imaging , Radiation Injuries/etiology , Radiography , Radiotherapy/adverse effects
17.
Eur J Radiol ; 16(3): 171-5, 1993 Apr.
Article in English | MEDLINE | ID: mdl-7685284

ABSTRACT

This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.


Subject(s)
Brain Neoplasms/diagnosis , Brain/pathology , Contrast Media , Dextrans , Iron , Magnetic Resonance Imaging/methods , Oxides , Animals , Antibodies, Monoclonal , Ferrosoferric Oxide , Humans , Lymphocytes , Rats , Rats, Nude , Tissue Distribution
18.
Magn Reson Med ; 29(1): 32-7, 1993 Jan.
Article in English | MEDLINE | ID: mdl-7678318

ABSTRACT

Human peripheral blood mononuclear cells (PBMCs) were incubated with large unilamellar vesicles (LUV) containing encapsulated dextran-magnetite particles (DMP). This resulted in an efficient incorporation of DMP. Electron microscopy revealed the presence of DMP in cells mainly in phagosomes and secondary lysosomes. DMP-labeled PBMCs showed a strong increase of the transverse relaxation rate (up to 16.6 s-1 for 5 x 10(7) cells/ml) and, accordingly, a great loss of signal intensity in MR imaging. The fraction of DMP containing PBMCs could be enriched by magnetic cell separation. The major population of the DMP containing cells proved to be monocytes. When PBMCs depleted of monocytes were used for labeling, DMP uptake was observed also in the peripheral blood lymphocytes. The labeling of PBMCs presented here may be used in future studies of selective MR imaging of in vivo cell migration in a variety of immunologically compromised tissue states, e.g., tumors, transplantations, and abscesses.


Subject(s)
Dextrans , Iron , Leukocytes, Mononuclear , Liposomes , Magnetic Resonance Imaging , Oxides , Contrast Media , Ferrosoferric Oxide , Humans , Leukocytes, Mononuclear/ultrastructure , Magnetic Resonance Spectroscopy
19.
J Biol Chem ; 266(9): 5593-9, 1991 Mar 25.
Article in English | MEDLINE | ID: mdl-1672314

ABSTRACT

In the present study we have analyzed the involvement of phosphorylation in the function of P-glycoprotein and have also examined sites of phosphorylation along the P-glycoprotein polypeptide chain. The results show that in HL60 cells isolated for resistance to vincristine the protein kinase inhibitor staurosporine induces a major inhibition in the phosphorylation of P-glycoprotein. Further studies show that under the same conditions in which staurosporine inhibits P-glycoprotein phosphorylation there is a concomitant increase in cellular drug accumulation and a major inhibition in drug efflux. Additional studies using pulse-chase experiments show that the P-glycoprotein phosphate groups are metabolically active and that the protein undergoes rapid cycles of phosphorylation and dephosphorylation in the cell. Structural analyses demonstrate that cleavage of 32P-labeled P-glycoprotein at Asp-Pro linkages with formic acid results in the formation of a major phosphorylated peptide of 35 kDa and a minor peptide of 42 kDa. Western blot analysis using site-specific anti-sera against P-glycoprotein suggests that P35 represents a phosphorylated fragment containing P-glycoprotein amino acids 446-744. Analysis of tryptic peptides using site-specific antisera identifies a second major phosphorylated region of P-glycoprotein which contains amino acids 745-1088. These studies thus suggest that phosphorylation plays an important role in the biological activity of P-glycoprotein. The results also indicate that two adjacent internal regions are highly phosphorylated in the P-glycoprotein molecule.


Subject(s)
Drug Resistance , Membrane Glycoproteins/metabolism , Vincristine/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Alkaloids/pharmacology , Amino Acid Sequence , Amino Acids/analysis , Blotting, Western , Cell Line , Electrophoresis, Polyacrylamide Gel , Formates/chemistry , Hydrolysis , Molecular Sequence Data , Phosphorylation , Precipitin Tests , Staurosporine , Trypsin/chemistry
20.
Biochim Biophys Acta ; 1022(1): 17-26, 1990 Feb 16.
Article in English | MEDLINE | ID: mdl-2154261

ABSTRACT

The effect of the hydrophobic Ca2+ ionophore, A23187, on the phospholipid dynamics of large unilamellar vesicle (LUVs: 4: 1 (w/w) mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG] membranes, as a function of A23187 content, was investigated using techniques sensitive to the phospholipid phase transition. The ultrasonic absorption per wavelength, alpha lambda, was determined with a double crystal acoustic interferometer, as a function of temperature and frequency for LUVs in the vicinity of their phospholipid phase transition. Differential scanning calorimetry (DSC) and electron spin resonance (ESR) were also employed to probe the thermodynamics and molecular environment of the hydrocarbon side chains. With increasing A23187 content, the phase transition temperature (Tm) of the LUV suspensions remained near 42.0 degrees C, while the amplitude of alpha lambda at the phase transition increased dramatically. At Tm the relaxation frequency, where alpha lambda max occurs, decreased with A23187 content, suggesting that the relaxation rate of the event responsible for the absorption of ultrasound decreased. The ESR studies showed no change in the fluidity of the bilayer with the inclusion of 2 and 5 mol% A23187 in the C-12 region of the bilayer. Therefore, A23187 in LUV membranes slows the structural relaxation of the hydrocarbon side chains of the phospholipid bilayer at the phase transition.


Subject(s)
Calcimycin/pharmacology , Lipid Bilayers , Phospholipids/metabolism , Ultrasonics , Calorimetry, Differential Scanning , Electron Spin Resonance Spectroscopy , Liposomes/metabolism , Temperature
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