Search PubMed⌕ Search

Biomedical subjects

D Webb

Publications and source records attributed to D Webb.

At least 55 records · Page 3Linked to original sources
PubMed1998

Haploidentical related transplants and unrelated donor transplants with T cell addback.

Only 30% of children have a matched family donor (MFD). Alternative donors can be found from volunteer unrelated donor (UD) panels, and almost every child has a haploidentical parental donor (Haplo). The outcome of alternative donor BMT has previously been inferior due to increased graft rejection and GVHD. The recent outcome of 121 consecutive children undergoing MFD, UD, and Haplo BMT between 1994 and 1997 was analysed. [table in text] Preparative regimens for MFD/UD/Haplo BMT respectively included TBI in 30%/36%/11%, chemotherapy only in 59%/64%/89%, Campath 1G or none n 14%/ 0%/0%. The balance of GVHD and rejection was addressed by T-cell depletion (Campath 1M) in 2/71 MFD BMTs, T-cell depletion with addback of 5 x 10(4) T cells/kg on day zero in 33/41 UD BMTs, and T cell depletion of purified mobilised peripheral blood CD34+ cells and bone marrow in 9/9 Haplo BMTs. Stable engraftment was achieved in 68/71, and 35/41 (one patient after 2nd BMT) and 7/9 MFD, UD, and Haplo BMTs respectively. Median follow up, survival, disease free survival and, death rates for MFD/UD/Haplo BMT were 12/12/12 months, 74%/77%/78%, 69%/67%/67%, and 27%/23%/23% respectively. Within a wide range of paediatric diseases the outcome of alternative donor BMT now parallels that of MFD BMT.

Adolescent↗
PubMed1997

T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6.

During development of CD4+ T lymphocytes in the periphery, differential expression of cytokine genes, such as those of interleukin (IL)-2 and IL-4, occurs in distinct T-cell subsets. IL-4 is a cytokine produced by T-helper 2 (Th2) cells, and the IL-4 receptor (IL-4R)-mediated signaling pathway is thought to be required for commitment to the Th2 phenotype. However, the molecular basis for development of the Th subset-specific production of IL-4 remains unclear. We demonstrate here that the IL-4 promoter is functional in Th1 and B cells which do not normally form IL-4 transcripts as well as in IL-4-producing T cells. Based on studies of the effect of several different upstream and downstream regions of the IL-4 gene on IL-4 promoter activity, a Th1-specific IL-4 silencer element was identified in the 3'-untranslated region. The silencer region contained a consensus sequence for a transcriptional factor that is normally regulated by the IL-4 R signaling pathway, STAT6. Nuclear expression of STAT6 protein, which was shown to bind to the silencer region, was observed in Th2 cells but not in Th1 cells. Deletion of the STAT6-binding site from the silencer region and inhibition of STAT6 function resulted in the appearance of silencing function even in Th2 cells. These results provide evidence that the silencer element, and the binding of STAT6 to this element, play a permissive role in determining the commitment into Th2 phenotype.

Animals↗
PubMed1997

Physiological role of the endothelin system in human cardiovascular and renal haemodynamics.

Based on studies with a number of endothelin antagonists, endothelin-1 is now known to play a key physiological role in the maintenance both of basal systemic vascular resistance and of blood pressure in healthy people. Factors that regulate activity of the vascular endothelin system, and its physiological effects on the heart and kidney, now need to be determined.

Cardiovascular Physiological Phenomena↗
PubMed1996

Maximum walking speed and lower limb length in hominids.

In 1984, Helene (Am.J. Physics 52:656) and Alexander (Am. Scientist 72:348-354) presented equations which purported to explain how lower limb length limited maximum walking speed in humans. The equations were based on a simplified model of human walking in which the center of mass (CoM) "vaults" over the supporting leg. Increasing walking speed by increasing stride frequency or stride length would increase the upward acceleration of the CoM in the first half of stance phase, to the point that it would be greater than the downward pull of gravity, and the individual would become airborne. This constitutes running by most definitions. While these models ignored various mechanical factors, such as knee flexion during midstance, that reduce the vertical movement of the CoM, the general idea is plausible inasmuch as the CoM of the body does oscillate vertically with each step. One hypothesis tested here is whether it is indeed the interaction between the pull of gravity and the individual's own upward acceleration that determines at what speed (or cadence) he changes from walking to running. Another hypothesis considered is that increased lower limb length (L) was selected for in early hominids, because of the locomotor advantages of longer lower limbs. Results indicate, however, that while L was clearly related to maximum possible walking speed, it was not an important factor in determining maximum "comfortable" walking speed. These and other results from the recent literature suggest that increased lower limb length provided no selective advantage in locomotion, and other explanations should be sought.

Adolescent↗
PubMed1996

Lack of B cells precursors in marrow transplant recipients with chronic graft-versus-host disease.

B cell reconstitution after bone marrow transplantation is slow in patients with chronic graft-vs.-host disease (cGVHD). Could this be secondary to decreased production of B cells in the bone marrow? We determined the relative amount of B cell precursors in the marrow of 26 patients at approximately 1 year after marrow transplant (10 patients with and 16 patients without clinical cGVHD) and 8 normal adult controls. In the controls (median), 3.1% of all marrow mononuclear cells were B cell precursors. The patients without cGVHD tended to have higher than normal percents of B cell precursors (median 6.5%; the difference from normal adults was not significant). In contrast, the patients with cGVHD had barely detectable B cell precursors (median 0.2%; the difference from normal adults was significant, P = 0.004). Therefore, delayed reconstitution of 8 cells in patients with cGVHD appears to be due at least in part to decreased B cell production by the marrow.

Antigens, CD34↗
PubMed1996

Audit in palliative care: does practice change?

This study aimed to document current palliative care initiatives, identify any reported changes in working practice as a result of audit, and determine the opinions of palliative care staff towards audit. All 31 established palliative care services within the former North West Thames Regional Health Authority were sent a brief postal questionnaire on previous and current audit activities. Of the 28 units who responded, most (78%, n = 21) were currently involved in audit with a further 7% (n = 2) planning to implement audit in the near future. Changes as a result of audit included implementation of standards, for example response to referrals; improvements in documentation, for example revision of case notes; and changes to unit practice, such as converting to multidisciplinary care plans. The respondents viewed the main advantage of carrying out any audit project as the improvement or maintenance of the quality of patient care. The principal disadvantage expressed was the time-consuming nature of audit. An audit with a clear aim and thorough design can provide valuable evidence upon which new policies or strategies in palliative care can be based. By educating and training staff in audit and illustrating the benefits, any concerns about carrying out audit could be addressed.

Attitude of Health Personnel↗
PubMed1996

Brucella abortus as a potential vaccine candidate: induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B. abortus.

Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells. B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation.

Antigens, CD↗
PubMed1995

B-cell non-Hodgkin's lymphoma presenting as a primary renal tumour in a child.

A 6-year-old boy presented with a unilateral renal tumour thought to be a Wilms' tumour. He had started a treatment but review of the histology and immunohistochemical studies proved the tumour to be a primary renal B-cell lymphoma. This case illustrates the importance of an open-minded approach in the histological examination of small round cell tumours in the kidney and immunohistochemical studies in such cases are strongly advocated.

Antigens, CD↗
PubMed1995

Measuring forearm blood flow and interpreting the responses to drugs and mediators.

Venous occlusion plethysmography has been widely used to study forearm blood flow. The principle of the technique is straightforward: the rate of swelling of the forearm during occlusion of venous return is used to assess the rate of arterial inflow. Provided that perfusion pressure (arterial blood pressure) remains constant, changes in flow reflect changes in smooth muscle tone in small arteries and arterioles. Local infusion into the brachial artery allows assessment of the direct effect of drugs on vascular tone and has been used to probe the roles of endogenous mediators. The technique is at its most powerful when dose-response relationships to different drugs or mediators within a single study are being compared but can also be used for comparison of responses to drugs between healthy control subjects and patient populations. However, when responses between groups are being compared, it is important to take into account the starting conditions of baseline blood flow and pressure. This article describes venous occlusion plethysmography, discusses the presentation and analysis of data (dose of drug or concentration? forearm blood flow or resistance?), and highlights certain potential problems and limitations of the technique as a means of studying disease states.

Blood Pressure↗