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Biomedical subjects

David Ritchie

Publications and source records attributed to David Ritchie.

8 recordsLinked to original sources

Autologous dendritic cells pulsed with eluted peptide as immunotherapy for advanced B-cell malignancies.

We have studied the feasibility, safety and efficacy of vaccination with autologous dendritic cells pulsed with eluted peptide in patients with advanced low-grade B-cell malignancies. This study demonstrates that autologous dendritic cell vaccines can be successfully produced from patients with advanced disease and be delivered without significant toxicity. Furthermore, we have demonstrated immunological and clinical responses in two of ten patients treated. These results provide further evidence for the use of immunotherapy in the management of B-cell malignancies, but also suggest that sustained responses may only be possible in patients with low bulk disease early in the disease course.

Adult↗

Prospective monitoring of tumor necrosis factor alpha and interferon gamma to predict the onset of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation.

Peripheral blood T cells were isolated from 19 allogeneic and 4 autologous stem cell transplant (SCT) recipients and assessed for tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma transcription by reverse transcription-polymerase chain reaction. Levels were compared with resting donor T-cell transcription levels. Increased production of TNF-alpha predicted for the onset of severe (grade II-IV) graft-versus-host disease (GVHD) (P = .001). Increased TNF-alpha (P = .025) and IFN-gamma (P = .001) transcription also independently predicted for the eventual onset of extensive chronic GVHD. Increased TNF-alpha or IFN-gamma transcription was not seen in either a syngeneic SCT recipient or 4 autologous SCT controls. These findings provide a means by which GVHD can be predicted before it is clinically evident, thus allowing for accurate diagnosis and monitoring of GVHD and possibly more cost-effective management of post-SCT immunosuppression.

Acute Disease↗

Reduced genetic variation occurs among genes of the highly clonal plant pathogen Xanthomonas axonopodis pv. vesicatoria, including the effector gene avrBs2.

The bacterial plant pathogen Xanthomonas axonopodis pv. vesicatoria, also known as Xanthomonas campestris pv. vesicatoria group A, is the causal agent of bacterial spot in pepper and tomato. In order to test different models that may explain the coevolution of avrBs2 with its host plants, we sequenced avrBs2 and six chromosomal loci (total of 5.5 kb per strain) from a global sample of 55 X. axonopodis pv. vesicatoria strains collected from diseased peppers. We found an extreme lack of genetic variation among all X. axonopodis pv. vesicatoria genomic loci (average nucleotide diversity, pi = 9.1 x 10(-5)), including avrBs2. This lack of diversity is consistent with X. axonopodis pv. vesicatoria having undergone a recent population bottleneck and/or selective sweep followed by population expansion. Coalescent analysis determined that approximately 1.4 x 10(4) to 7.16 x 10(4) bacterial generations have passed since the most recent common ancestor (MRCA) of the current X. axonopodis pv. vesicatoria population. Assuming a range of 50 to 500 bacterial generations per year, only 28 to 1,432 years have passed since the MRCA. This time frame coincides with human intervention with the pathogen's host plants, from domestication to modern agricultural practices. Examination of 19 mutated (loss-of-function) avrBs2 alleles detected nine classes of mutations. All mutations affected protein coding, while no synonymous changes were found. The nature of at least one of the avrBs2 mutations suggests that it may be possible to observe one stage of an evolutionary arms race as X. axonopodis pv. vesicatoria responds to selection pressure to alter avrBs2 to escape host plant resistance.

Alleles↗

Early and late infectious consequences of adding rituximab to fludarabine and cyclophosphamide in patients with indolent lymphoid malignancies.

Whether the addition of rituximab to fludarabine and cyclosphosphamide (FC) increases early or late infection risk remains poorly defined. This retrospective analysis of 160 patients treated with FC+/-rituximab found no evidence of increased infection among patients receiving FC+rituximab, providing some evidence of safety for the continued exploration of this regimen.

Adult↗

Terahertz emission from quantum cascade lasers in the quantum Hall regime: evidence for many body resonances and localization effects.

A terahertz quantum cascade laser, operating at lambda=159 microm and exploiting the in-plane confinement arising from perpendicular magnetic field, is used to investigate the physics of electrons confined on excited subbands in the regime of a large ratio of the magnetic field confinement energy to the photon energy. As the magnetic field is increased above about 6 T, and the temperature lowered below 20 K, the devices are characterized by a very low threshold current density, with values as low as J(th)=1A/cm(2), and an increase of gain by five times the low field value. We show that, as with the quantum Hall effect, the key physical process is the localization of the carriers. Evidences for resonant electron-electron scattering processes are directly obtained from light intensity and transport measurements.

Journal Article↗

Terahertz quantum cascade lasers.

Recent developments in terahertz quantum cascade lasers are reviewed. Structures operating from a wavelength of lambda = 66 microm down to lambda = 87 microm are demonstrated. These devices used either a three-quantum-well chirped-superlattice active region or an active region based on a bound-to-continuum transition. The comparison between structures grown in a waveguide based on a single interface plasmon and a buried contact and (non-lasing) structures using a double plasmon waveguide demonstrates the importance of waveguide design on the operation of such devices. Continuous-wave operation up to a maximum temperature of 55 K with up to 15 mW output power at 10 K was demonstrated.

Journal Article↗

Application of terahertz quantum-cascade lasers to semiconductor cyclotron resonance.

Quantum-cascade lasers operating at 4.7, 3.5, and 2.3 THz have been used to achieve cyclotron resonance in InAs and InSb quantum wells from liquid-helium temperatures to room temperature. This represents one of the first spectroscopic applications of terahertz quantum-cascade lasers. Results show that these compact lasers are convenient and reliable sources with adequate power and stability for this type of far-infrared magneto-optical study of solids. Their compactness promises interesting future applications in solid-state spectroscopy.

Journal Article↗

Graft-versus-lymphoma effects: clinical review, policy proposals, and immunobiology.

The indubitable existence of a graft-versus-lymphoma (GVL) effect is difficult to prove directly. This article reviews the difficulties in interpreting the current literature in this field and, with a number of caveats, argues for the existence of a clinically meaningful GVL effect in follicular, mantle cell, small lymphocytic, and Hodgkin lymphomas. The evidence, however, for a potent GVL effect in diffuse large-cell lymphoma and Burkitt lymphoma is not convincing. Policies for allografting in lymphoma are proposed on the basis of this evidence. The immunobiology of GVL effects is discussed--in particular, the expression of HLA class I and II and co-stimulatory molecules on lymphomas that influence the generation of alloreactive T cells--together with future directions in immunotherapy that may help to eradicate chemoresistant disease.

Graft vs Tumor Effect↗