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Biomedical subjects

R Jarrett

Publications and source records attributed to R Jarrett.

11 recordsLinked to original sources

Hodgkin's disease in the elderly: current status and future directions.

In general, it was agreed that high rates of toxicities during treatment occur in the elderly and that there is a frequent occurrence of early relapse. It is clear that different combinations of effective therapies with lower toxicity are required. It was felt, however, that certainly in the 60-70 year age group, approaches should be vigorous to and the same diagnostic and staging procedures as in younger individuals, but with much closer monitoring of toxicity and response to treatment. It was felt that as part of the approach, liberal support with haemopoeitic growth factors (G-CSF) was necessary to reduce prolonged neutropenia. It is important to understand that age in general is not a contrary indication for aggressive treatment and that biologically younger patients under the age of 65 years, in good physical and mental condition, often should be given with stage-adapted treatment, analogous to conventional treatment protocols for the <60 years age group. It was also considered that, in patients who clearly could not accept conventional treatment, study groups could begin to define the best palliative care for patients with pre-existing organ impairment, and that in all situations of assessment, whether in trial or not, there should be a detailed prospective assessment of quality of life parameters.

Adult↗

HV(MNE), a novel lymphocryptovirus related to Epstein-Barr virus, induces lymphoma in New Zealand White rabbits.

HV(MNE) is a novel Epstein-Barr (EBV)-like virus isolated from a Macaca nemestrina with CD8(+) T-cell mycosis fungoides-cutaneous T-cell lymphoma. Here it is demonstrated that intravenous inoculation of irradiated HV(MNE)-infected T cells or cell-free virus from the J94356(PBMC) cell line in New Zealand White rabbits results in seroconversion to the viral capsid antigen (VCA) of EBV; all animals that seroconverted to VCA developed malignant lymphoma within months of inoculation. In contrast, control rabbits, inoculated with heat-inactivated culture supernatants from the same cell line, failed to seroconvert to VCA and did not develop disease. Disseminated lymphoma cells of mixed origin were detected in most vital organs, including the spleen, liver, lungs, kidneys, and heart of the affected rabbits. Neoplastic infiltrates were also observed in lymph nodes, thymus, skin, and subcutaneous tissues. HV(MNE) DNA and EBV-like RNA expression was demonstrated in the lymphomatous organs and in 2 transformed T-cell lines, one established from the lymph node and the other from the blood of the 2 lymphomatous animals. Analysis of one of these T-cell lines demonstrated the persistence of HV(MNE) DNA, expression of an LMP1-like protein, and acquisition of interleukin-2 independence, and constitutive activation of the Jak/STAT pathway. Thus, HV(MNE) in rabbits provides a valuable animal model for human T-cell lymphoma whereby genetic determinants for T-cell transformation by this EBV-like animal virus can be studied.

Animals↗

Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami.

OBJECTIVE: To determine whether regional cerebral blood flow (rCBF) is abnormal in any cerebral structure of women with fibromyalgia (FM), following a report that rCBF is reduced in the thalami and heads of caudate nuclei in FM. METHODS: Seventeen women with FM and 22 healthy women had a resting single-photon-emission computed tomography (SPECT) brain scan to assess rCBF and a T1-weighted magnetic resonance imaging (MRI) scan to enable precise anatomic localization. Additionally, all participants underwent 2 manual tender point examinations and completed a set of questionnaires evaluating clinical features. SPECT scans were analyzed for differences in rCBF between groups using statistical parametric mapping (SPM) and regions of interest (ROIs) manually drawn on coregistered MRI. RESULTS: Compared with control subjects, the rCBF in FM patients was significantly reduced in the right thalamus (P = 0.006), but not in the left thalamus or head of either caudate nucleus. SPM analysis indicated a statistically significant reduction in rCBF in the inferior pontine tegmentum (corrected P = 0.006 at the cluster level and corrected P = 0.023 for voxel of maximal significance), with consistent findings from ROI analysis (P = 0.003). SPM also detected a reduction in rCBF on the perimeter of the right lentiform nucleus. No correlations were found with clinical features or indices of pain threshold. CONCLUSION: Our finding of a reduction in thalamic rCBF is consistent with findings of functional brain imaging studies of other chronic clinical pain syndromes, while our finding of reduced pontine tegmental rCBF is new. The pathophysiologic significance of these changes in FM remains to be elucidated.

Analysis of Variance↗

Increased frequency of HLA-DPB1*0301 in Hodgkin's disease suggests that susceptibility is HVR-sequence and subtype-associated.

Hodgkin's disease (HD) is a complex lymphoma-like disease which occurs as four main subtypes, nodular sclerosing (NS), mixed cellularity (MC), lymphocyte predominant (LP) and lymphocyte depleted (LD). Suggestions from epidemiological studies that HD may represent an unusual response to infection imply that the lack of previous response could be due to genetic factors. Following recent reports suggesting that there is an increased frequency of HLA-DPB1*0301 in Hodgkins disease, we have studied DPB1 in two series of patients using molecular typing methods. One series is a retrospective group of 118 patients over the age of 15 years from a single centre, and the other is a multi-centre prospective group of 45 patients between the age of 16 and 24 years. In both series, the percentage of HD patients with DPB1*0301 is greater than in the controls, confirming that this seems to be an HD-susceptibility allele. However, extension of the analysis in relation to HD subtype shows that the increase in *0301 is present in nodular sclerosing (NS), mixed cellularity (MC) and lymphocyte predominant patients (LP) HD patients, but preliminary evidence suggests an increase in *0401, and possibly *0501 in MC- and LP-HD. The DPB1 hypervariable region (HVR) amino-acid motif Asp55, Glu56 (*0301-like, HVR-C) is increased in NS compared with non-NS (ie MC+LP), whereas the frequency of Ala55, Ala56 (*0401-like) is increased in non-NS compared with NS. Conversely, Asp84, Glu85Ala86(*0301-like, HVR-F) motif is more frequent in NS than non-NS patients, but there is no increase in Gly84, Gly855, Pro86 (*0401-like). These findings suggest that genetic susceptibility in HD may reside at the level of HVR-encoded DPB1 peptide-binding residues, rather than with a specific allele, and that this may in some way influence the HD subtype.

Adolescent↗

Nucleotide sequence of transforming human c-sis cDNA clones with homology to platelet-derived growth factor.

Three c-sis cDNA clones were obtained from polyadenylated RNA of a human T-cell lymphotropic virus (HTLV) type I transformed cell line. Two clones, designated pSM-1 and pSM-2, have cDNA inserts of 2498 and 2509 base pairs (bp), respectively, excluding the sizes of the guanylate tails, and the polyadenylate tracts. These clones are shorter than the estimated size of the c-sis mRNA of 4200 bp. Both of these clones can transform NIH 3T3 cells. The third clone, designated pSM-3 has a cDNA insert of 1421 bp and lacks transforming activity. The sequence of clone pSM-1 reveals a single long open reading frame (nucleotides 118-840) encoding chain A of platelet-derived growth factor, and two segments with homology to v-sis (nucleotides 182-871 and 1021-1325). Sequence homology is noted in the 3' untranslated region to the corresponding regions of the beta 1 interferon (IFN), human and murine beta-nerve growth factor (NGF), human interleukin 2 (IL2) genes, and tubulin pseudogenes. However, no typical AATAAA polyadenylation signal is present. An alternating (dCdA)n X (dGdT)n sequence is present in the 3' flanking cellular sequences similar to those in the corresponding position of the human proenkephalin gene, in the first intron of the gamma-IFN gene, and the second intron of the beta-NGF gene.

Animals↗

The Salmon structure.

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Nursing Service, Hospital↗

An improved screening system for the early detection of congenital dislocation of the hip.

A screening programme for congenital dislocation of the hip in which physiotherapists examine all neonates is described, together with the results over a 7-year period. All easily reducible dislocated and dislocatable hips are splinted within 2-5 days of birth. Subluxable or "slidey" hips are identified and followed up but not splinted. Risk groups are also identified and followed up. There was a progressive decrease in the number of late diagnosed cases, a result suggesting that even late-presenting acetabular dysplasia can be eliminated by neonatal screening.

England↗