Reliability of structural parameters determined from DAFS data using the iterative dispersion integral algorithm.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L B Sorensen.
Explore the source record for details and available documents.
Diffraction anomalous fine-structure (DAFS) experiments measure Bragg peak intensities as continuous functions of photon energy near a core-level excitation. Measuring the integrated intensity at each energy makes the experiments prohibitively slow; however, in many cases DAFS can be collected quickly by measuring only the peak intensity at the center of the rocking curve. A piezoelectric-actuator-driven stage has been designed and tested as part of a sample-angle feedback circuit for locking onto the maximum of the rocking curve while the energy is scanned. Although software peak-tracking requires only a simple calculation of diffractometer angles, it is found that the additional hardware feedback dramatically improves the reproducibility of the data.
Though the principle may seem simple or fundamental it has been our experience that the best way to develop clinician-educators in an academic setting is to value their contributions. This means that those contributions must lead to promotion, they should be valued by colleagues, they must be valued by the administration and the chairman, and they must be considered when determining faculty salary. As faculty members perceived that they were valued for teaching and clinical service. and would not be punished for the amount of time they were spending in these endeavors, there was a clear group of faculty who came forward to take on a primary teaching role. This group was not limited to general pediatricians or ambulatory pediatricians, but included some specialists who felt that their pediatric background was sufficient for them to teach in a primary care setting. Two of our leading teachers in the generalist curriculum are specialists in nephrology and hematology/oncology. Although this requires them to go back and increase their knowledge in general pediatrics, it is far less difficult according to these faculty members than they expected. Our specialists continue to maintain their specialty practices, but have oriented their didactic lectures and clinical teaching to specialty and general aspects of pediatrics. It is not difficult to teach about parenting and psychosocial skills when describing a complicated specialty patient and to orient the students and residents to the general care of such a patient. Although the majority of strategies described in this article deal with departmental and college initiatives, the reason that these strategies have become an integral part of the Department of Pediatrics is the changing health care environment in Nebraska. Managed care has mandated that physicians be more flexible and be willing to take on a primary care role within their specialty. This has made the transition for many faculty much easier and has been reinforced by financial reimbursement for their services. The transition would not have been as easy had there been no movement of the community toward primary care, or no shift in the university's interest in primary care as a mechanism for providing sufficient patient numbers to fulfill our teaching missions. Clinical research has become the area of focus for many of the primary care physicians and some specialists in the past few years, and the university is in the process of developing a clinical research center to allow for outpatient studies. Although the strategies summarized are specific to the University of Nebraska Medical Center, many of the principles could be adapted to other teaching programs. The most basic element is to tie reward and recognition to efforts in primary care.
Synovial fluid from 33 patients with inflammatory arthritis was examined with a polarized light microscope (PLM) and an atomic force microscope (AFM). Two samples were imaged with a transmission electron microscope (TEM) to determine calcium/phosphate ratios and identify microcrystals of calcium pyrophosphate dihydrate and octacalcium phosphate. Additional correlative x-ray diffraction studies were performed on several samples including purified hydroxyapatite and sodium chloride crystals. Monosodium urate, calcium pyrophosphate dihydrate, hydroxyapatite, octacalcium phosphate, and cholesterol crystals were identified with AFM. AFM images of these microcrystals revealed detailed surface topology, including lattice parameters and structural irregularities at the crystals' surface. These features were consistent with those obtained by TEM and x-ray diffraction studies. In addition, AFM images revealed that some specimens contained microcrystals that were undetected by PLM and/or TEM. These results suggest that AFM may provide a simple yet powerful technique for the detection of microcrystals in synovial fluid taken from patients with crystal-induced arthritis.
Explore the source record for details and available documents.
The prevalence of rheumatic diseases was studied in representative subsamples by interview (n = 134), and by physical (n = 89) and radiographic (n = 81) examination in a representative sample of 79-year-olds in Göteborg, Sweden. The prevalence of rheumatoid arthritis (3-8 ARA criteria) was 10%. Radiographic osteoarthritis (OA) was diagnosed in wrists and/or finger joints of 65% of the probands and in knee joints of 14%. The first metacarpophalangeal (MCP I) joint was more frequently involved in males than in females (p less than 0.05). In females palpable enlargement of distal (DIP) and proximal interphalangeal finger joints correlated (p less than 0.01) to radiographic OA. The degree of heavy work in previous occupations was correlated to radiographic OA of DIP II-V in females (p less than 0.05 and of MCP I in males (p less than 0.05) but not to radiographic or clinical OA in knee joints. Symptoms of OA were reported by 6.1% in the knee and in 4.5% in hip joints. The prevalence of chondrocalcinosis averaged 15% (23% of females and 6% of males). Chondrocalcinosis of the hands occurred in 21% of females but in no males. The prevalence of hyperuricemia was 15% (women 6%, men 29%), and gouty arthritis was found in one woman.
The prevalence of back and joint impairments was studied in a representative subsample of 77 women and 57 men aged 79. Forty-six per cent of the subjects had no history of back or joint complaints. Thirty-two per cent reported current back pains while 50% stated they never experienced such pains. Back pains (past or present) were localized in the lumbar region predominantly (40%), and were almost constantly present in 8% of the subjects. The spinal mobility remained acceptable for function of the activities of daily living (ADL) in the majority of the subjects. Thirty-six per cent of the subjects had past or present complaints from the joints of the extremities, predominantly of the knee, shoulder or hip joints. Physical signs of joint disorders as deformities, swelling or tenderness were rare except for enlargement of distal interphalangeal joints (right hand: females 38%, males 14%). Restricted range of motion (ROM) in one or several joints was found in one fifth (i.e., knee joints) to two thirds (i.e., hip joints). No significant gender differences were observed with the exception of the thoracolumbar ROM that was more frequently restricted in males. Severe restriction of separate movements (to less than 50% of ROM) was, generally, infrequent (0-8% of the subjects) although advanced impairment of hip inward rotation was found in 14% of the subjects. Restricted ROM associated with joint complaints was found in 2-11% of the subjects (i.e., knee joints 2%, shoulder joints 9%, hip joints 11%). A considerable proportion of 79-year-olds, thus, had some--though usually limited--restriction of joint ROM.
The incidence and significance of positive cutaneous immunofluorescence findings were assessed in biopsy specimens of both sun-exposed and non-sun-exposed skin of 34 adult patients with rheumatoid arthritis (RA) who were not receiving systemic corticosteroids. The incidence of lupus erythematosus (LE)-band was low (8.6%) in both groups. Twenty-eight percent of the patients had perivascular IgM and/or C3 deposits, and 74% had cytoid bodies in the papillary dermis. These studies indicate that the incidence of LE band is low in RA and that the detection of such a band in normal skin warrants close follow-up of RA patients for possible development of LE.
Explore the source record for details and available documents.
Proteins are dynamic systems. Recent evidence demonstrates that they exist in a large number of conformational substates and can continuously move from one substate to another; motion of a small ligand inside a protein may be possible only through these conformational fluctuations. To test this idea, we study with flash photolysis the binding of CO to protoheme and O2 and CO to myoglobin in many different solvents. The standard evaluation of such experiments yields information only about the protein-solvent system. A novel approach is presented which permits conclusions concerning the protein: Data from all solvents are considered together, and the rates for transitions of the ligand over various barriers are studied as a function of temperature for fixed solvent viscosities. Results show that over a wide range in viscosity the transition rates in heme-CO are inversely proportional to the solvent viscosity and can consequently be described by the Kramers equation. The rates of O2 and CO in myoglobin also depend on the solvent viscosity and are most sensitive to the solvent at the lowest viscosity. Viscosity influences protein reactions even in aqueous solutions. The data dan be interpreted by a dynamic model in which transitions into and inside myoglobin are governed by fluctuations between conformational substates corresponding to closed and open pathways. Ligand motion thus is mainly controlled by gates and not by static potential barriers. Some characteristic parameters for the substates are determined, and they agree approximately with similar parameters found in Mössbauer experiments. As expected, the barrier parameters evaluated in the novel approach deviate markedly from the ones obtained by the conventional procedure. Comparison with model calculations or basic theories will be meaningful only with the new evaluation, and the method may be essential for many or possibly all biochemical reactions.
Explore the source record for details and available documents.
Bidirectional renal urate tranport was studied in both control and gouty subjects. 99.3% of filtered urate undergoes reabsorption as assessed by pyrazinamide suppression of urate secretion. The maximum uricosuric response to benzbromarone, equated with the minimum secretory rate, amounted to 50% of the filtered load in normal persons and was lower in gouty normoproducers. Since benzbromarone selectively inhibits reabsorption of secreted urate, the difference between secreted and excreted uric acid becomes a valid measure of urate reabsorption distal to the secretory site and amounts to 80% of the secreted load in both groups. These data conform to a 4-component model of renal urate handling in man.
A 26-year-old woman was found to have an abnormally sensitive excretory response to a rise in plasma urate with a markedly increased ratio of uric acid to creatinine clearance (exceeding 35%). Uric acid was studied before and after administration of pyrazinamide and benzbromarone. In the presence of pyrazinamide urinary uric acid decreased markedly just as in normal subjects. The uricosuric response to benzbromarone was reduced. No other renal tubular or metabolic abnormalities were found. It appears that the abnormality is related to an isolated defect in postsecretory reabsorption of urate.
The replacement reaction of myoglobin (Mb), MbCO + O2 leads to MbO2 + CO leads to MbCO + O2, has been studied with flash photolysis in the temperature range from 140 to 320 K and the time range from 2 mus to 200 s. In a fraction of the Mb, the photodissociated CO remains within the protein; rebinding is not affected by the presence of O2 and occurs with rates that are identical with the ones observed earlier in solvents containing only CO. In the remaining fraction CO migrates into the solvent and Mb combines preferentially with oxygen. The rate of the subsequent replacement of O2 by CO permits calculation of the oxygen dissociation rate ko2; ko2 has been determined from 260 to 320 K. The measurements support a multibarrier model.
Shulman's syndrome includes fasciitis of rapid onset, sclerodermoid skin changes, absence of Raynaud's phenomenon, absence of visceral manifestations of progressive systemic sclerosis, hypergammaglobulinemia, transient eosinophilia, and a dramatic response to systemic corticosteroid therapy. Although this syndrome may be a variant of scleroderma, its dramatic responsiveness to corticosteroid therapy is a particularly distinguishing feature.
Binding of carbon monoxide to the separated alpha and beta chains of hemoglobin, with and without bound p-mercuribenzoate, has been measured at temperatures from 5 to 340 K for times 2 mus to 1 ks using flash photolysis. All four proteins exhibit three different rebinding processes. The data are interpreted by a model in which the carbon monoxide, moving from the solvent to the binding site at the ferrous heme iron, encounters three barriers. The temperature dependences of the three processes yield activation enthalpies and entropies for the three barriers for all four proteins. Binding at temperatures below about 200 K is nonexponential, implying that the innermost barrier has a distribution of activation enthalpies. The distributions for the four proteins have been determined. At temperatures below 30 K, the CO binding rates approach finite low-temperature limits; binding thus proceeds by quantum-mechanical tunneling. Invoking a simple model, the widths of the innermost barriers are extracted from the measured tunneling rates. The experimental parameters are correlated with structural features of the hemoglobin chains and compared with previously published data on myoglobin and protoheme. A correlation is established between the height of the innermost barrier and the equilibrium CO pressure.
Using fast flash photolysis, we have measured the binding of CO to carboxymethylated cytochrome c and to heme c octapeptide as a function of temperature (5 degrees-350 degreesK) over an extended time range (100 ns(-1) ks). Experiments used a microsecond dye laser (lambda = 540 nm), and a mode-locked frequency-doubled Nd-glass laser (lambda = 530 nm). At low temperatures (5 degrees-120 degreesK) the rebinding exhibits two components. The slower component (I) is nonexponential in time and has an optical spectrum corresponding to rebiding from an S = 2, CO-free deoxy state. The fast component (I*) is exponential in time with a lifetime shorter than 10 mus and an optical spectrum different from the slow component. In myoglobin and the separated alpha and beta chains of hemoglobin, only process I is visible. The optical absorption spectrum of I* and its time dependence suggest that it may correspond to recombination from an excited state in which the iron has not yet moved out of the heme plane. The temperature dependences of both processes have been measured. Both occur via quantum mechanical tunneling at the lowest temperatures and via over-the-barrier motion at higher temperatures.
Explore the source record for details and available documents.