Update on rituximab.
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Biomedical subjects
Publications and source records attributed to R Eisenberg.
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Three new di-tert-butylbipyridine (dbbpy) complexes of platinum(II) (1-3) containing 1,1-dithiolate ligands have been synthesized and characterized. The 1,1-dithiolates are 2,2-diacetylethylene-1,1-dithiolate (S(2)C=C(C(O)Me)2) (1), 2-cyano-2-p-bromophenylethylene-1,1-dithiolate (S(2)C=C(CN)(p-C(6)H(4)Br)) (2), and p-bromophenyl-2-cyano-3,3-dithiolatoacrylate (S(2)C=C(CN)(COO-p-C(6)H(4)Br)) (3). Complex 1 exhibits a solvatochromic charge-transfer absorption in the 430-488 nm region of the spectrum and a luminescence around 635 nm in ambient temperature CH(2)Cl(2) solution. These observations are consistent with what has been seen previously in related Pt diimine 1,1-dithiolate complexes. The nature of the emissive state is assigned as a (3)(mixed metal/dithiolate-to-diimine) charge transfer, while the solvatochromic absorption band corresponds to the singlet transition of similar orbital character. The other complexes also exhibit a low-energy solvatochromic absorption. The crystal structures of two of the complexes have been determined, representing the first time that Pt(diimine)(1,1-dithiolate) complexes have been crystallographically studied. The structures confirm the expected square planar coordination geometry with distortions in bond angles dictated by the constraints of the chelating ligands. The Pt-S and Pt-N bond lengths and S-Pt-S and N-Pt-N bond angles for the two structures are identical within experimental error (2.283(2) and 2.278(2) A; 2.053(6) and 2.050(8) A; 75.01(8) degrees and 75.40(8) degrees; 79.2(2) degrees and 79.0(2) degrees, respectively). Crystal data for 1: monoclinic, space group P2(1)/n (No. 14), with a = 7.20480(10) A, b = 20.53880(10) A, c = 19.1072(2) A, beta = 93.83 degrees, V = A(3), Z = 4, R1 = 3.34% (I > 2sigma(I)), wR2 = 9.88% (I > 2sigma(I)) for 3922 unique reflections. Crystal data for 2: monoclinic, space group P2(1)/n (No. 14), with a = 15.0940(5) A, b = 9.5182(3) A, c = 20.4772(7) A, beta = 111.151(1) degrees, V = A(3), Z = 4, R1 = 4.07% (I > 2sigma(I)), wR2 = 8.64% (I > 2sigma(I)) for 3859 unique reflections.
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OBJECTIVE: We describe the clinical presentation and the radiographic and CT findings of benign metastasizing leiomyoma. CONCLUSION: Benign metastasizing leiomyoma is an asymptomatic disease characterized by well-defined, numerous, pulmonary lesions without a preponderant distribution.
The mononuclear Au(I) complex, Au(Spy)(PPh2py) (1), has been synthesized and characterized structurally. The complex possesses the expected linear coordination geometry with a S-Au-P bond angle of 176.03(6) degrees and no evidence of aurophilic interactions between nearest neighbor Au(I) ions in the solid state. Protonation of the pendant pyridyl groups of 1 leads to the formation of the H-bonded dimer [(Au(SpyH)(PPh2py))2](PF6)2 (2), which has also been structurally characterized. A linear coordination geometry at the Au(I) ions in 2 with a S-Au-P bond angle of 173.7(2) degrees is augmented by evidence of a strong aurophilic interaction with a Au...Au distance of 2.979(1) A. The pendant pyridyl groups of 1 have also been used to bind Cu(I) by reactions with [Cu(NCMe)4](PF6) and Cu(P(p-tolyl)3)2(NO3) leading to the formation of the heterobimetallic complexes [(AuCu(mu-Spy)(mu-PPh2py))2](PF6)2 (3) and [AuCu(P(p-tolyl)3)2(mu-Spy)(mu-PPh2py)](NO3) (4), respectively. A structure determination of 3 reveals a tetranuclear complex composed of two AuCu(mu-Spy)(mu-PPh2py)+ units held together by bridging thiolate ligands. A strong metal-metal interaction is noted between the two different d10 ions with nearest Au-Cu distances averaging 2.6395 A. The S-Au-P bond angles in 3 deviate slightly from linearity due to the Au...Cu interactions, while the coordination geometries at Cu(I) are distorted tetrahedral consisting of the two pyridyl nitrogen atoms, a bridging thiolate sulfur, and the interacting Au(I) ion. While mononuclear complex 1 is only weakly emissive in the solid state and in fluid solution, complexes 2-4 show stronger photoluminescence in the solid state and rigid media at 77 K, and in fluid solution. The emission maxima for 2-4 in ambient temperature fluid solution are 470, 635, and 510 nm, respectively. A tentative assignment of the emitting state as a S(p pi)-->Au LMCT transition is made on the basis of previous studies of Au(I) thiolate phosphine complexes. Shifts of lambda em result from the influence of H bonding or Cu(I) coordination on the filled thiolate orbital energy, or on the effect of metal-metal interaction on the Au(I) acceptor orbital energy. Crystal data for Au(Spy)(PPh2py) (1): triclinic, space group P1 (No. 2), with a = 8.3975(4) A, b = 11.0237(5) A, c = 12.4105(6) A, alpha = 98.6740(10) degrees, beta = 105.3540(10) degrees, gamma = 110.9620(10) degrees, V = 995.33(8) A3, Z = 2, R1 = 3.66% (I > 2 sigma(I)), wR2 = 9.04% (I > 2 sigma(I)) for 2617 unique reflections. Crystal data for [(Au(SpyH)(PPh2py))2](PF6)2 (2): triclinic, space group P1 (No. 2), with a = 14.0284(3) A, b = 14.1093(3) A, c = 15.7027(2) A, alpha = 97.1870(10) degrees, beta = 96.5310(10) degrees, gamma = 117.1420(10) degrees, V = 2692.21(9) A3, Z = 2, R1 = 7.72% (I > 2 sigma(I)), wR2 = 15.34% (I > 2 sigma(I)) for 5596 unique reflections. Crystal data for [(AuCu(mu-Spy)(mu-PPh2py))2](PF6)2 (3): monoclinic, space group P2(1)/c (No. 14), with a = 19.6388(6) A, b = 16.3788(4) A, c = 17.2294(5) A, beta = 91.48 degrees, V = 5540.2(3) A3, Z = 4, R1 = 3.99% (I > 2 sigma(I)), wR2 = 8.38% (I > 2 sigma(I)) for 10,597 unique reflections.
A new set of luminescent platinum(II) diimine complexes has been synthesized and characterized. The anionic ligands in these complexes are arylacetylides. The complexes are brightly emissive in fluid solution with relative emission quantum yields phiem ranging from 3 x 10(-3) to 10(-1). Two series of complexes have been investigated. The first has the formula Pt(Rphen)(C...CC6H5)2 where Rphen is 1,10-phenanthroline substituted in the 5-position with R = H, Me, Cl, Br, NO2, or C...CC6H5, while the second has the formula Pt(dbbpy)(C=CC6H4X)2 where dbbpy = 4,4'-di(tert-butyl)bipyridine and X = H, Me, F, or NO2. From NMR, IR, and electronic spectroscopies, all of the complexes are assigned a square planar coordination geometry with cis-alkynyl ligands. The crystal structure of Pt(phen)(Ce-CC6H4CH3)2 confirms this assignment. All of the complexes exhibit an absorption band at ca. 400 nm that corresponds to a Pt d-->pi*diimine charge-transfer transition. The variation of lambdamax for this band with substituent variation supports this assignment. From similar changes in the energy of the solution luminescence as a function of substituents R and X, the emissive excited state is also of MLCT origin, but with spin-forbidden character on the basis of excited-state lifetime measurements (0.01-5.6 micros). The complexes undergo electron-transfer quenching, showing good Stern-Volmer behavior using 10-methylphenothiazine and N,N,N',N'-tetramethylbenzidine as reductive quenchers. Excited-state reduction potentials are estimated on the basis of a simple thermochemical analysis. Crystal data for Pt(phen)(C...CC6H4CH3)2: monoclinic, space group C2/c, a = 19.0961(1) A, b = 10.4498(1) A, c = 11.8124(2) A, beta = 108.413(1) degrees, V = 2236.49 A3, number of reflections 1614, number of variables 150, R1 = 0.0163, wR2 (I > 2sigma) = 0.0410.
Understanding the basic forces that determine molecular recognition helps to elucidate mechanisms of biological processes and facilitates discovery of innovative biotechnological methods and materials for therapeutics, diagnostics, and separation science. The ability to measure interaction properties of biological macromolecules quantitatively across a wide range of affinity, size, and purity is a growing need of studies aimed at characterizing biomolecular interactions and the structural elements that drive them. Optical biosensors have provided an increasingly impactful technology for such biomolecular interaction analyses. These biosensors record the binding and dissociation of macromolecules in real time by transducing the accumulation of mass of an analyte molecule at the sensor surface coated with ligand molecule into an optical signal. Interactions of analytes and ligands can be analyzed at a microscale and without the need to label either interactant. Sensors enable the detection of bimolecular interaction as well as multimolecular assembly. Most notably, the method is quantitative and kinetic, enabling determination of both steady-state and dynamic parameters of interaction. This article describes the basic methodology of optical biosensors and presents several examples of its use to investigate such biomolecular systems as cytokine growth factor-receptor recognition, coagulation factor assembly, and virus-cell docking.
Our laboratory has utilized spontaneous and experimentally induced models of systemic autoimmunity in mice in order to elucidate the cellular deficiencies in immunoregulation that are essential to this process. In the spontaneously autoimmune mouse strains, genetic defects in T and B cell tolerance are the primary abnormalities that drive the syndrome. The induced chronic graft-vs-host model depends on abnormal T-B interactions resulting from allogeneic recognition of major histocompatibility complex (MHC) class II. Future investigations will target the biochemistry of the loss of tolerance and the specificity of autoreactive T cells that provide help for autoantibody production.
From January 1969 to December 1992, mitral valve reconstructive operations were performed on 155 patients with degenerative mitral valve disease. There were 102 male and 53 female patients, with a mean age of 60.5 +/- 9.2 years, a mean duration of symptoms of 3.8 +/- 2.7 years, and 34% were in atrial fibrillation. All patients were in New York Heart Association functional classes III and IV before operation. The degree of mitral regurgitation was severe in 94% and moderate in 6%, and 50.9% of patients had moderate to severe impairment of left ventricular function. Emergency operation was undertaken in 7.1% of cases; 19% of patients underwent additional procedures. All patients had posterior mitral leaflet pathology and 19 patients had anterior mitral leaflet pathology. Ring annuloplasty was used in only 3% of cases. The operative mortality rate was 3.9%, 9% of patients had morbid events, and 4.5% of patients had repair failure within 6 months. All patients have been followed up with serial echocardiography for a mean time of 5.2 +/- 0.3 years (range 0.5 to 24 years). Immediately after operation, 92.9% had no mitral regurgitation to mild mitral regurgitation. At last follow-up, 96.9% had no mitral regurgitation to mild mitral regurgitation by echocardiography and 98% of patients were in New York Heart Association functional classes I and II. The actuarial survival at 15 years was 46% +/- 11%, freedom from reoperation was 84.9% +/- 11%, freedom from infective endocarditis was 96.0% +/- 11%, freedom from thromboembolism was 90.4% +/- 11%, and freedom from all valve-related events was 36.7% +/- 11%. It is well documented that repair of degenerative mitral valves offers excellent short-term and medium long-term benefits. This series represents the longest follow-up reported outside Europe. Our results beyond 10 years support our conclusion that an annuloplasty ring is not an absolute prerequisite for achieving successful repair of proven durability in most patients with degenerative mitral valve disease.
To document the outcome of vestibular nerve section from the patient's point of view we reviewed 102 patients who had undergone vestibular nerve section 1 to 10 years after operation. Only 3 patients had experienced further vertigo attacks: 2 of these were cured by a further, this time translabyrinthine vestibular nerve section; 1 patient developed multiple sclerosis. In contrast, about 50% of patients developed some subjective problem with balance while standing or walking; in 15% it was present all the time and of moderate severity. Despite this, over 85% of patients reported that they felt much better or back to normal after the operation and were satisfied with the outcome. The development and application of objective preoperative measures of vestibular and, in particular, vestibulospinal function might improve patient selection for vestibular nerve section and thus reduce the number of dissatisfied patients.
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The reaction path and free energy profile of Na+ were computed in the interior of the channel protein gramicidin, with the program MOIL. Gramicidin was represented in atomic detail, but surrounding water and lipid molecules were not included. Thus, only short range interactions were investigated. The permeation path of the ion was an irregular spiral, far from a straight line. Permeation cannot be described by motions of a single Na+ ion. The minimal energy path includes significant motion of water and channel atoms as well as motion of the permeating ion. We think of permeation as motion of a permion, a quasi-particle that includes the many body character of the permeation process, comparable with quasi-particles like holes, phonons, and electrons of solid-state physics. Na+ is accompanied by a plug of water molecules, and motions of water, Na+, and the atoms of gramicidin are highly correlated. The permion moves like a linear polymer made of waters and ion linked and moving coherently along a zigzag line, following the reptation mechanism of polymer transport. The effective mass, free energy, and memory kernel (of the integral describing time-dependent friction) of short range interactions were calculated. The effective mass of the permion (properly normalized) is much less than Na+. Friction varies substantially along the path. The free energy profile has two deep minima and several maxima. In certain regions, the dominant motions along the reaction path are those of the channel protein, not the permeating ion: there, ion waits while the other atoms move. At these waiting sites, the permion's motion along the reaction path is a displacement of the atoms of gramicidin that prepare the way for the Na+ ion.
STUDY OBJECTIVES: To determine the concordance of emergency physicians and radiologists in interpreting cranial computed tomography (CT) scans. The study also sought to determine the clinical significance of misinterpretations of cranial CT scans by emergency physicians. DESIGN: Prospective cohort study. SETTING: A county hospital emergency medicine residency program. PARTICIPANTS: Five hundred fifty-five patients undergoing CT scanning during emergency department evaluation. RESULTS: Forty-nine percent (272) of the indications for CT scanning were for trauma, 14.2% (79) were for cerebrovascular accident, 25.1% (139) were for headache, 15.1% (84) were for seizure, and 13.7% (76) were for miscellaneous reasons. The radiologists interpreted 46.1% (256) of the CT scans as abnormal. The most frequent abnormalities were scalp hematoma, 15.2% (39); infarction, 14.1% (36); calcification, 6.3% (16); contusion, 6.3% (16); parenchymal hemorrhage, 5.1% (13); and mass, 5.1% (13). Nonconcordance between radiologists and emergency physicians was found in 38.7% (206) of the cases. Potentially clinically significant misinterpretations were found in 24.1% (131) of the total sample. These misinterpretations included 62 missed major findings (11.4% of total sample): 25 new infarcts, 10 mass lesions, 8 cases of cerebral edema, 8 parenchymal hemorrhages, 5 contusions, 4 subarachnoid hemorrhages, 1 epidural hematoma, and 1 subdural hematoma. However, on chart review, only three patients (0.6%) were found to have been managed inappropriately, and none had an adverse outcome. CONCLUSION: The misinterpretation rate of cranial CT scans by emergency physicians is of potential clinical concern. However, clinical mismanagement is rare. We recommend that more formal education in CT interpretation be included in residency training and continuing medical education programs for emergency physicians.
"Immortal is his work. Immortal his name." This dedication to Wilhelm Roentgen, the discoverer of x-rays, is much deserved. As a meticulous scientist, Roentgen devised and repaired all the apparatus needed for his experiments, and he did most of the work himself.
In order to explore the development of self-evaluative biases, children at 3 age levels (5-6, 7-8, 9-10) evaluated themselves or another child when given social or temporal comparison feedback. Evaluative biases were indicated by higher evaluations for the self than another, especially after failure. Children at different ages were not differentially responsive to temporal vs. social comparison information. However, evaluative bias in response to the type of evaluation differed by age; there was greater bias for general ability evaluations by older children and greater bias for specific performance evaluations by younger children. Alternative explanations for these self-other differences were minimized, as differences in visual orientation were held constant and differences in knowledge of effort were controlled statistically. Other aspects of the design as well as sex differences support a motivational interpretation of these biases. How these biases are manifested is related to children's level of understanding and concerns at different ages.
Certain autoimmune mouse strains exhibit features similar to human SLE. To discover genetic and immunologic events governing expression of a new SLE-associated antibody, the presence of anti-Su and its relationship to other SLE-related antibodies (anti-Sm, -ribonucleoprotein, -Ro (SS-A), -La (SS-B)) were determined in MRL and other autoimmune and nonautoimmune mice. By double immunodiffusion, sera from 34/183 (19%) 4- to 10-mo-old MRL/Mp-lpr/lpr (MRL/lpr) and 28/108 (26%) 8- to 20-mo-old MRL/Mp(-)+/+ (MRL/+) mice were positive for anti-Su antibodies. Anti-Sm antibodies were found in 60/183 (33%) and 39/108 (36%) of these animals, respectively. The two specificities were found together in individual mice more frequently than would be predicted by chance. In contrast, C57BL/6-lpr/lpr (B6/lpr) mice rarely showed either specificity. Analysis of F1 hybrids between B6/lpr and MRL/lpr and of F1 x MRL/lpr backcross mice suggested that a small number of autosomal recessive genes controlled the anti-Su and anti-Sm responses. With the exception of a single NZB serum sample, NZB, BXSB, and nonautoimmune mice were negative for all antibodies tested, and no mice were positive for anti-RNP, anti-Ro, or anti-La. MRL/lpr and MRL/+ autoimmune mice thus provide unique models for human SLE, because they express several of the SLE-specific marker autoantibodies. These models should be useful in disclosing molecular and immunologic events governing autoantibody expression in this condition.