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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 91 records · Page 5Linked to original sources

Generation of T cells from cytokine-mobilized peripheral blood and adult bone marrow CD34+ cells.

The present study compared the T-cell progenitor content of CD34+ lineage (Lin)- cells isolated from normal adult bone marrow (ABM) and mobilized peripheral blood (MPB). Both cell populations were found to differentiate into T cells when injected into human fetal thymi implanted into severe combined immunodeficient mice. Cytokine-MPB cells were less efficient than ABM cells in engrafting in the fetal human thymus, although both gave rise to thymocytes with identical phenotypes based on the analysis of CD1a, CD3, CD4, and CD8 expression. Thymocytes derived from adult CD34+ Lin- cells were capable of fully differentiating into mature CD3+ T cells expressing either the T-cell receptor (TCR) gamma delta or the TCR alpha beta (the later associated with CD4 or CD8), showing that the T-cell progenies of adult CD34+ cells were polyclonal and functional. Our data indicate that human MPB CD34+ cells are qualitatively identical to their BM counterparts, and demonstrate the existence of T-lymphoid progenitor cell activity in MPB.

Adult

Dr Know.

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Communication

Stem cell factor enhances the survival of irradiated human bone marrow maintained in SCID mice.

The effect of recombinant human stem cell factor (SCF) on the response of human fetal bone marrow progenitor cells to irradiation was studied using immunodeficient mice with human fetal bone grafts (SCID/Hu mice). SCID/Hu mice were treated with three intraperitoneal injections of 500 micrograms/kg SCF at 20 h before, two h before, and four h after 100 cGy total body irradiation. Fourteen days following irradiation, the fetal bone grafts were harvested and studied. Most of the isolated bone marrow cells were human, as determined by flow cytometry. Colony forming assays were performed on the bone marrow to determine the survival of erythroid (BFU-E) and myeloid (CFU-GM) precursor cells. A statistically significant increase in BFU-E and CFU-GM survival after irradiation was observed for bone marrow maintained in the SCF treated mice when compared to bone marrow from mice not treated with SCF. The enhancement in colony forming unit survival after irradiation ranged from 4.3-fold for BFU-E (p = 0.05) to 13.1-fold for CFU-GM (p = 0.002). These findings suggest that SCF may be of potential clinical value for the prevention of radiation-induced myelosuppression.

Animals

A linkage map of microsatellite markers on the human X chromosome.

The efficiency of mapping and diagnosis of X-linked disorders by linkage depends upon the existence of a high-density genetic map of polymerase chain reaction (PCR)-based markers. DXS1120, DXS1122, DXS1123, DXS1124, DXS1125, DXS1126, and DXS1153 were randomly isolated from a flow-sorted lambda bacteriophage library of the human X chromosome. The CCN (N = A or G) repeat within the androgen receptor was also found to be polymorphic and primers were designed for genotyping the CCN polymorphism in addition to the AGC polymorphism. The above markers, together with microsatellite polymorphisms at DXS237 (GMGX9), 5'DYS-II and 3'DYS MS (within the dystrophin locus), DXS538 (XL27B), PGK1P1, DXS300 (VK29AC), DXS294 (VK17AC), and DXS102 (cX38.1AC), were genotyped in the 40 CEPH reference families. One marker, DXS1153, was found to include cryptic alleles that amplify only in homozygotes and hemizygotes but not heterozygotes. A PCR-based linkage map was constructed using all of the above markers plus PCR-based markers from the CEPH database and those PCR-based markers previously typed in our laboratory: ALAS2, DXS292 (VK14AC), DXS297 (VK23AC), FRAXAC1, and FRAXAC2. The genetic map of the X chromosome incorporates 62 PCR-based marker loci, integrates the Weissenbach markers, and extends from XG near Xpter to DXS52 near Xqter, a distance of 236 cM.

Alleles

A comparison of proton and megavoltage X-ray treatment planning for prostate cancer.

Conformal photon and proton therapy plans for prostate cancer have been compared in an attempt to quantify the potential advantages of using protons. Two X-ray plans (3-field, 6-field) and a 2-field proton plan were made and compared for each of 20 T3 prostate patients with the aid of the 3D planning system VOXELPLAN. Dose distributions were analysed in terms of dose-volume histograms (DVH). Tumour control probability (TCP) and normal tissue complication probability (NTCP) were computed using our own and the Lyman-Kutcher-Burman models, respectively. The study shows that on average the proton technique results in the best dose distribution, giving the lowest rectal complication probability, and also that the 3-field X-ray technique is more effective than the 6-field X-ray technique in sparing the rectum. At 5% rectal NTCP, the predicted proton average TCP for the 20 patients is 2% (in absolute terms) greater than that obtained using 3-field X-ray therapy. For 7 of the patients the gain in TCP is more than 3%. For the same rectal NTCP as the 3-field X-ray plan with a 64 Gy mean target dose, the use of protons increases the TCP by 2% on average, but for 5 of the patients the increases are greater than 4%. The result is in general positive towards the use of protons but a few patients do not benefit from it and this indicates the importance of patient selection for maximum clinical benefit.

Humans

Perceptions and practices of registered nurses regarding pastoral care and the spiritual need of hospital patients.

Reports the findings of a questionnaire survey designed to examine the impact of pastoral care on patient care and job satisfaction of registered nurses (N-280) employed in a metropolitan hospital. Suggests that educational strategies be explored as a way of broadening the perspectives of nurses regarding reasons for consulting pastoral care departments.

Attitude of Health Personnel

Prescribing and referral in general practice: a study of patients' expectations and doctors' actions.

BACKGROUND: What decisions do patients expect the general practitioner to take within the consultation and to what extent are these expectations fulfilled? What factors influence patients' expectations and general practitioners' actions? AIM: This study aimed to examine these questions with reference to prescribing and hospital referral. METHOD: The study covered 1080 consultations with 12 general practitioners in two north London practices. Information was collected by self-administered questionnaires from patients before the consultation and from the general practitioners after the consultation. RESULTS: Fifty one per cent of patients expected and 55% received a prescription; 13% expected hospital referral and 10% were referred. Factors related to their presenting problem were most strongly associated with patients' expectation of receiving a prescription. The actions which the general practitioners took were most strongly associated with patients' expectations. Patients' anxiety about their health problem also appeared to influence their expectations of referral and the doctor's prescribing decision. CONCLUSION: This study suggests that patients' expectation of management and their anxiety associated with the presenting problem may be two of the factors which influence general practitioners' prescribing and referral behaviour and may explain some of the observed variations in behaviour.

Adolescent

Is determination of creatine kinase-2 after electrophoretic separation accurate?

Since 1991, the Ontario Laboratory Proficiency Testing Program has assessed the analytical performance of creatine kinase (CK; EC 2.7.3.2) isoenzyme-2, using fresh human serum supplemented with purified human CK isoenzymes. In Ontario, the 142 laboratories licensed to analyze CK-2 use a variety of methods: electrophoresis-based, immunoinhibition, and mass assays. During a 1992 survey, duplicate CK-2 samples with different total CK activities showed poorer precision when analyzed after electrophoretic separation than by any other method. A 1993 survey designed to validate these observations conclusively showed that electrophoresis-based assays are subject to a bias proportional to the total CK activity. These survey results were confirmed by studies with selected patients' specimens. We therefore conclude that electrophoresis-based assays may not warrant their reputation as the gold standard for CK isoenzyme measurement.

Creatine Kinase

Inheritance of a meiotic abnormality that causes the ovulation of primary oocytes and the production of digynic triploid mice.

Previous studies have demonstrated that the LT/SvKau strain of mice ovulates a high proportion of oocytes as diploid primary oocytes rather than secondary oocytes. These ovulated primary oocytes are arrested at meiotic metaphase I but may be fertilized to produce digynic triploid embryos. In the present study, 40.4% of eggs analysed from LT/SvKau females were ovulated as primary oocytes, compared to 1.2% from control C57BL/Ws strain mothers. These two inbred strains were intercrossed to produce eight sets of F1, F2 and backcross females and the frequency of triploidy was investigated. The results are compatible with segregation of a co-dominant, autosomal gene that has a major influence on the incidence of triploidy. We suggest that the provisional gene symbol Poo (primary oocyte ovulation) be assigned to this gene, with alleles Poo(l) (the 'mutant' allele present in the LT/SvKau strain) and Poo(b) (the normal allele present in C57BL/Ws mice). Poo is incompletely penetrant and has variable expressivity because the proportion of oocytes ovulated as primary oocytes by LT/SvKau mice was variable and, in some cases, nil. In putative Poo(l)/Poo(b) heterozygotes the frequency of ovulated primary oocytes was increased only marginally (from 1.2% to 6.6%) by the presence of one copy of the Poo(l) allele, but this increase was found consistently (in two reciprocal F1 crosses) and was statistically significant. No evidence was found for tight genetic linkage between Poo and two Mendelian loci (brown on chromosome 4 and glucose phosphate isomerase on chromosome 7), that were segregating in the crosses. The Poo(l) mutant in the LT/SvKau strain of mice provides a valuable resource to study the cell and molecular biology of mammalian oocyte maturation and the control of meiosis.

Alleles

The effect on tumour control probability of varying the setting of a multileaf collimator with respect to the planning target volume.

The multileaf collimator (MLC) is being used increasingly to replace Cerrobend blocks when shaping radiation fields. When the MLC has a stepped edge in relation to the planning target volume (PTV) there might be concern that the MLC is not equivalent to the use of a block. This concern is countered by studying the effect on the tumour control probability of varying the distance between the stepped edge of the MLC and the contour of the PTV. It is observed that provided an adequate margin is added to the PTV when using the MLC the TCP is not reduced. The meaning of adequate has been accurately quantitated as being > or = 7 mm when the projected leaf width is 10 mm at the isocentre. This is the margin which when added to the outline of the planning target volume will ensure no reduction in TCP compared with the use of a block.

Humans

A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density.

Most calculations of the biological effect of radiation on tumours assume that the clonogenic cell density is uniform even if account is taken of non-uniform dose distribution. In practice tumours will almost certainly have a non-uniform clonogenic cell density. This paper extends one particular model of tumour control probability (TCP) to incorporate a variable clonogenic cell density while at the same time assuming a constant 2 Gy fraction size and a uniform radiosensitivity throughout the treatment. Since there are virtually no in vivo data on the variation of density we consider some model situations. One clear conclusion is that a large reduction in clonogenic cell density at the edges of a tumour would permit only a very modest decrease in dose if the TCP is not to be reduced. In general the effect on TCP is a complicated function of the variation in both dose and clonogenic cell density. We give the equations which enable both to be included.

Cell Count

Non-attendance at outpatient clinics: is it related to the referral process?

Non-attendance at outpatient clinics is a complex problem and previous studies have concentrated on hospital-related factors. It has been suggested that non-attendance might be related to the referral process, including the selection of patients for referral and the quality of communication between GP and patient. These issues are examined in a study of 1492 patients given first-time appointments at ENT and gastroenterology clinics. Non-attendance rates were 26 and 20% respectively. Non-attendance was not related to the nature, severity or duration of the patients' presenting problems at the time of referral or to their perception of the need for referral. Resolution of symptoms did not appear to be a major reason for non-attendance. Patients were significantly less likely to attend if they had been unable or only partly able to discuss their health problem with their general practitioner. Those who had requested referral were equally likely to default.

Adult

An autoantigenic T cell epitope forms unstable complexes with class II MHC: a novel route for escape from tolerance induction.

The peptide rAc1-11 represents the dominant T cell epitope of rat myelin basic protein (MBP) in mice of the H-2u haplotype. Residue 4 has been shown previously to govern binding of the peptide to the class II molecule, I-Au. We have constructed peptide analogues bearing amino acid substitutions at position 4 and have assessed their ability to stimulate an antigen-specific T cell hybridoma when presented by viable antigen presenting cells (APC). Complexes between I-Au and one such analogue, rAc1-11[4A], were rapidly lost from the surface of live APC displaying a half-life (t 1/2) of approximately 10 min. Neither shedding of intact complexes from the cell surface, nor their internalization and recycling through an acidic intracellular compartment were found to account for their loss. The possible dissociation of rAc1-11[4A] from the peptide binding cleft was therefore addressed by comparing the t 1/2 of complexes between I-Au and peptide analogues of higher affinity. The tyrosine-substituted analogue, rAc1-11[4Y], remained stably bound to I-Au for at least 4 h, thereby displaying a t 1/2 far in excess of that evident for rAc1-11[4A]. Significantly, the wild type peptide, rAc1-11, bound so transiently that functional complexes could not be detected on the surface of peptide-pulsed APC. The physiological relevance of these findings was confirmed by extending our studies to an analysis of the homologous epitope of murine MBP; evidence that this epitope likewise displays minimal affinity for I-Au suggests a novel strategy for the escape from tolerance induction by encephalitogenic T cells.

Amino Acid Sequence

A prospective evaluation of the hepatotoxicity of lofepramine in the elderly.

Lofepramine has been acclaimed as an effective and safe antidepressant, particularly for the elderly. Recent case reports of hepatic toxicity following treatment with lofepramine, however, caused clinicians to question its use in a patient population who frequently have concomitant physical illness. From published data the incidence of serious side effects as well as the implications for its use remain unclear. In this study, 52 patients over the age of 65 years treated with lofepramine were monitored over a 12-week period. The results suggest that for the overwhelming majority of patients, any rise in liver enzyme activity is transient. It is recommended, however, that LFTs be monitored for the first 12 weeks of treatment.

Aged