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Biomedical subjects

A Freiberg

Publications and source records attributed to A Freiberg.

At least 19 recordsLinked to original sources
PubMed2001

Effector function of resting T cells: activation of synovial fibroblasts.

Synovial tissue in rheumatoid arthritis is characterized by infiltration with large numbers of T lymphocytes and APCs as well as hyperplasia of synovial fibroblasts. Current understanding of the pathogenesis of RA includes the concept that synovial fibroblasts, which are essential to cartilage and bone destruction, are regulated by cytokines derived primarily from monocyte-macrophage cells. Recently it has been found that synovial fibroblasts can also function as accessory cells for T cell activation by superantigens and other stimuli. We have now found that highly purified resting T cells, even in the absence of T cell mitogens, induce activation of synovial fibroblasts when cocultured for 6-24 h. Such activation was evident by induction or augmentation of mRNA for stromelysin, IL-6, and IL-8, gene products important in joint inflammation and joint destruction. Furthermore, increased production of IL-6 and IL-8 was quantitated by intracellular cytokine staining and flow cytometry. This technique, previously used for analysis of T cell function, was readily adaptable for assays of synovial fibroblasts. Resting T cells also induced synovial fibroblasts to produce PGE(2), indicating activation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells that activates fibroblasts, and resting T lymphocytes. Various subsets of T cells, CD4(+), CD8(+), CD45RO(+), and CD45RA(+) all had comparable ability to induce synovial fibroblast activation. These results establish an Ag-independent effector function for resting T cells that is likely to be important in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.

Adjuvants, Immunologic↗
PubMed2001

Effect of high pressure on the photochemical reaction center from Rhodobacter sphaeroides R26.1.

High-pressure studies on the photochemical reaction center from the photosynthetic bacterium Rhodobacter sphaeroides, strain R26.1, shows that, up to 0.6 GPa, this carotenoid-less membrane protein does not loose its three-dimensional structure at room temperature. However, as evidenced by Fourier-transform preresonance Raman and electronic absorption spectra, between the atmospheric pressure and 0.2 GPa, the structure of the bacterial reaction center experiences a number of local reorganizations in the binding site of the primary electron donor. Above that value, the apparent compressibility of this membrane protein is inhomogeneous, being most noticeable in proximity to the bacteriopheophytin molecules. In this elevated pressure range, no more structural reorganization of the primary electron donor binding site can be observed. However, its electronic structure becomes dramatically perturbed, and the oscillator strength of its Q(y) electronic transition drops by nearly one order of magnitude. This effect is likely due to very small, pressure-induced changes in its dimeric structure.

Bacteriochlorophylls↗
PubMed1998

The effect of pressure on the bacteriochlorophyll a binding sites of the core antenna complex from Rhodospirillum rubrum.

In this paper we examine the effect of pressure on the absorption spectrum and binding site of the core antenna complex from the photosynthetic bacterium Rhodospirillum rubrum. Absorption spectra and Raman spectra in preresonance with the Qy transition of the bacteriochlorophyll a were studied at pressures up to 625 MPa. In agreement with previous work we observe a pressure-induced red shift and broadening of the absorption spectrum. We show that at these pressures the pigments within the protein matrix at room temperature experience little if any distortion, and the hydrogen-bonding network involving the C2 and C9 carbonyl groups of the pigment molecules are undisturbed. Having shown the lack of sensitivity to pressure of the binding site interactions, which are known to modulate the absorption spectrum, we feel that it is relatively safe to attribute the pressure-induced red shift broadly to solvatochromic effects and, in particular, to the modulation of the pigment-pigment interactions by the pressure. This paper represents the first vibrational study of photosynthetic complexes at high pressure and the first application of FT Raman spectroscopy to biological molecules at high pressure.

Bacterial Proteins↗
PubMed1998

Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP.

Adolescent↗
PubMed1997

Electron transfer and electronic energy relaxation under high hydrostatic pressure.

The following question has been addressed in the present work. How external high (up to 8 kbar) hydrostatic pressure acts on photoinduced intramolecular electron transfer and on exciton relaxation processes? Unlike phenomena, as they are, have been studied in different systems: electron transfer in an artificial Zn-porphyrin-pyromellitimide (ZnP-PM) supramolecular electron donor-acceptor complex dissolved in toluene measured at room temperature; exciton relaxation in a natural photosynthetic antenna protein called FMO protein measured at low temperatures, between 4 and 100 K. Spectrally selective picosecond time-resolved emission technique has been used to detect pressure-induced changes in the systems. The following conclusions have been drawn from the electron transfer study: (i) External pressure may serve as a potential and sensitive tool not only to study, but also to control and tune elementary chemical reactions in solvents; (ii) Depending on the system parameters, pressure can both accelerate and inhibit electron transfer reactions; (iii) If competing pathways of the reaction are available, pressure can probably change the branching ratio between the pathways; (iv) The classical nonadiabatic electron transfer theory describes well the phenomena in the ZnP-PM complex, assuming that the driving force or/and reorganisation energy depend linearly on pressure; (v) A decrease in the ZnP-PM donor-acceptor distance under pressure exerts a minor effect on the electron transfer rate. The effect of pressure on the FMO protein exciton relaxation dynamics at low temperatures has been found marginal. This may probably be explained by a unique structure of the protein [D.E. Trondrud, M.F. Schmid, B.W. Matthews, J. Mol. Biol. 188 (1986) p. 443; Y.-F. Li, W. Zhou, E. Blankenship, J.P. Allen, J. Mol. Biol., submitted]. A barrel made of low compressibility beta-sheets may, like a diving bell, effectively screen internal bacteriochlorophyll a molecules from external influence of high pressure. The origin of the observed slow pico = and subnanosecond dynamics of the excitons at the exciton band bottom remains open. The phenomenon may be due to weak coupling of phonons to the exciton states or/and to low density of the relevant low-frequency ( approximately 50 cm(-1)) phonons. Exciton solvation in the surrounding protein and water-glycerol matrix may also contribute to this effect. Drastic changes of spectral, kinetic and dynamic properties have been observed due to protein denaturation, if the protein was compressed at room temperature and then cooled down, as compared to the samples, first cooled and then pressurised.

Journal Article↗
PubMed1997

Exciton dynamics in FMO bacteriochlorophyll protein at low temperatures.

A time response over almost 5 decades (from 10(-13) to about 10(-8) s) to a (sub)picosecond laser pulse excitation has been observed in the Fenna, Matthews, and Olson (FMO) antenna protein trimer. The FMO protein is unique in having a fine-structured bacteriochiorophyll a Qy exciton absorption spectrum over the whole investigated temperature range between 6 and 160 K. As measured by a two-color pump-probe differential absorption, the population decay of the exciton states of seven strongly coupled bacteriochlorophyll a molecules in a protein monomer is the dominant dynamical process in the subpicosecond time domain. The through-band scattering takes a few picoseconds and depends only weakly on temperature, probably because of a low density of exciton states. At low temperatures, evidence for a slow pico-nanosecond relaxation process has also been obtained via time-dependent red-shift and broadening of the exciton emission spectrum. Two nonexclusive tentative interpretations to this effect have been provided. The phenomenon may be due to exciton solvation in the surrounding protein and water-glycerol matrix or/and due to slow scattering of closely spaced bacteriochlorophyll a exciton states in a protein trimer. The shape of the excited-state absorption spectrum (arising from transitions between singly and doubly excited exciton states) and its oscillator strength has been roughly estimated from the analysis of the pump-probe spectrum. The spectrum peaks at around 805 nm and is less featured compared to the ground-state absorption spectrum. Both spectra have comparable strength.

Bacterial Proteins↗
PubMed1997

Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count.

To evaluate diagnostic criteria, disease characteristics, and the clinical course of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's Research Hospital between February 1980 and January 1993. Among 49 cases with <30% marrow blasts (consistent with FAB criteria and common diagnostic practice for MDS), eight had karyotypes associated with de novo AML (four with t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21), t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast count (AML-LBC) and compared their clinical and morphologic features with those of the remaining 41 cases. AML-LBC cases had little or no hematopoietic dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or multilineage hematopoietic dysplasia, with significantly higher dysplasia scores than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete remission (CR) after two cycles of AML-directed therapy, compared with 88% of patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23% +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients frequently had chloromas; none were seen in MDS patients. We conclude that the 30% blast threshold is ineffective for separation of AML and MDS in pediatric patients, and that genetic data should be included in this decision process. AML-LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic abnormalities associated with de novo AML, and characterized by absent or mild marrow dysplasia, is biologically and clinically distinct from MDS and should be treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment strategies are needed for these patients.

Acute Disease↗
PubMed1997

Are patients satisfied with results from residents performing aesthetic surgery?

An 8-year survey of patient satisfaction in an academic aesthetic surgery clinic at the University of Toronto was carried out by means of a mailed questionnaire. A total of 265 questionnaires were mailed; 131 completed questionnaires (49.4 percent) were returned. Of these, 93.1 percent would recommend this clinic (88.1 percent in the first year of operation and 95.4 percent in the subsequent 7 years), and 92.9 percent would undergo the same procedure again, if required (88.3 percent in the first year and 95.0 percent in the next 7 years). The highest patient satisfaction (10 of 10) was seen in augmentation mammoplasty (average, 9.1); blepharoplasty (average, 9.0); rhytidectomy (average, 7.8), and rhinoplasty (average, 6.9). The results obtained compared favorably with recently published data of more experienced surgeons.

Adolescent↗
PubMed1997

MRI interaction with tattoo pigments: case report, pathophysiology, and management.

A case is reported in which the presence of a decorative tattoo resulted in pain and termination of an MRI study. The ferromagnetic nature of the tattoo and iron oxide tattoo pigments is demonstrated. The pathophysiology of tattoo/MRI interaction is discussed, as is an approach to the prevention and treatment of this complication.

Adult↗
PubMed1996

Antenna size dependent exciton dynamics in the chlorosomal antenna of the green bacterium Chloroflexus aurantiacus.

Using picosecond fluorescence spectroscopy, we demonstrated antenna size dependent exciton dynamics in chlorosomal antenna, measured for intact cells of different cultures of the green bacterium Chloroflexus aurantiacus with different chlorosomal antenna size determined by electron microscopic examination of ultrathin sections of the cells. The measured bacteriochlorophyll (BChl) c excitation lifetimes show a quasilinear dependence on chlorosome size as predicted in our model for cylindrical exciton migration within the three-dimensional chlorosomal antenna. The migration model was developed for the proposed exciton model of chlorosomal BChl c aggregation. The data predict the time constant values for excitation energy transfer between BChl c aggregates as well as to BChl a of the baseplate.

Bacteria↗
PubMed1996

Excitation energy transfer in chlorosomes of green bacteria: theoretical and experimental studies.

A theory of excitation energy transfer within the chlorosomal antennae of green bacteria has been developed for an exciton model of aggregation of bacteriochlorophyll (BChl) c (d or e). This model of six exciton-coupled BChl chains with low packing density, approximating that in vivo, and interchain distances of approximately 2 nm was generated to yield the key spectral features found in natural antennae, i.e., the exciton level structure revealed by spectral hole burning experiments and polarization of all the levels parallel to the long axis of the chlorosome. With picosecond fluorescence spectroscopy it was demonstrated that the theory explains the antenna-size-dependent kinetics of fluorescence decay in chlorosomal antenna, measured for intact cells of different cultures of the green bacterium C. aurantiacus, with different chlorosomal antenna size determined by electron microscopic examination of the ultrathin sections of the cells. The data suggest a possible mechanism of excitation energy transfer within the chlorosome that implies the formation of a cylindrical exciton, delocalized over a tubular aggregate of BChl c chains, and Forster-type transfer of such a cylindrical exciton between the nearest tubular BChl c aggregates as well as to BChl a of the baseplate.

Bacteriochlorophylls↗
PubMed1995

Sporotrichosis of the hand: an urban experience.

Sporotrichosis is uncommon in Canadian urban centers. Lymphocutaneous and fixed cutaneous are the most common cutaneous forms of the disease, typically seen in the upper extremity in adult patients. History usually reveals a puncture injury contaminated with soil. Lesions are refractory to commonly used antibiotics. Cultures of biopsy specimens reliably grow the fungus Sporothrix schenkii. First line treatment is oral potassium iodide. We have reviewed a series of 7 cases from various Toronto teaching hospitals and compared them to the world literature.

Adult↗
PubMed1994

Energy transfer in the inhomogeneously broadened core antenna of purple bacteria: a simultaneous fit of low-intensity picosecond absorption and fluorescence kinetics.

The excited state decay kinetics of chromatophores of the purple photosynthetic bacterium Rhodospirillum rubrum have been recorded at 77 K using picosecond absorption difference spectroscopy under strict annihilation free conditions. The kinetics are shown to be strongly detection wavelength dependent. A simultaneous kinetic modeling of these experiments together with earlier fluorescence kinetics by numerical integration of the appropriate master equation is performed. This model, which accounts for the spectral inhomogeneity of the core light-harvesting antenna of photosynthetic purple bacteria, reveals three qualitatively distinct stages of excitation transfer with different time scales. At first a fast transfer to a local energy minimum takes place (approximately 1 ps). This is followed by a much slower transfer between different energy minima (10-30 ps). The third component corresponds to the excitation transfer to the reaction center, which depends on its state (60 and 200 ps for open and closed, respectively) and seems also to be the bottleneck in the overall trapping time. An acceptable correspondence between theoretical and experimental decay kinetics is achieved at 77 K and at room temperature by assuming that the width of the inhomogeneous broadening is 10-15 nm and the mean residence time of the excitation in the antenna lattice site is 2-3 ps.

Bacterial Chromatophores↗
PubMed1994

Osteoarthritis of the thumb: clinical aspects and management.

The wide range of motion of the thumb derives from the unusual nature of its carpometacarpal joint. Osteoarthritis is common in this joint. Patients may present with variable degrees of pain, reduction of thumb mobility, and joint deformity. Management is based on clinical assessment. Early disease is treated with rest, anti-inflammatory agents or analgesics, intraarticular steroid injections and splints. Since the course of osteoarthritis is often benign, avoiding early invasive treatment is important, except in the presence of proven anatomic deformity.

Humans↗
PubMed1994

Facial fractures.

Emergency room physicians frequently see facial fractures that can have serious consequences for patients if mismanaged. This article reviews the signs, symptoms, imaging techniques, and general modes of treatment of common facial fractures. It focuses on fractures of the mandible, zygomaticomaxillary region, orbital floor, and nose.

Diagnosis, Differential↗
PubMed1993

Picosecond dynamics of excitations in light-harvesting complex B800-850 from Chromatium minutissimum studied using fluorescence spectrochronography.

The picosecond dynamics of excitations in the isolated B800-850 light-harvesting complex of the purple sulfur bacterium Chromatium minutissimum has been studied using picosecond fluorescence spectrochronography. A short-lived component of about 20 ps lifetime has been found at 77K at the short wavelength part of the B850 fluorescence spectrum similar to that previously described for the core antenna bacteriochlorophyll band B880 of Rhodospirillum rubrum. Evidence has been presented indicating that this component is likely to reflect excitation energy relaxation step(s) involving both photoexcited bacteriochlorophyll and the protein environment. A new kinetic scheme of excitation transfer from the peripheral antenna to the photoreceptor units in purple bacteria is suggested which takes into account these findings.

Absorption↗