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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 235 records · Page 13Linked to original sources

Cytokine regulation of C3 and C5 production by human corneal fibroblasts.

Recent investigations have suggested that cytokines play important roles during inflammation and host defense, primarily by regulating the diverse functions of immunologic cells (e.g. lymphocytes and monocytes). However, much less is known about the capacity of cytokines to also regulate the functions of resident tissue cells. We hypothesize that during inflammation, cytokines (e.g. monokines and lymphokines) directly regulate the expression of inflammatory precursors and mediators, such as the third and fifth complement components, by resident ocular cells and are therefore important in the local regulation of ocular inflammation. To test this hypothesis we developed an in vitro culture system utilizing isolated human corneal fibroblasts and examined the effects of specific cytokines, i.e. interleukins and interferons, on the production of the third and fifth components of the complement system. Human corneal fibroblasts were cultured in the presence of varying concentrations (1-500 U ml-1) of interleukin 1 alpha, interleukin 1 beta, interleukin 2, interferon alpha and interferon gamma for 48 hr at 37 degrees C, 5% CO2. The supernatants were then evaluated for antigen levels for the third and fifth components of complement using specific enzyme-linked immunospecific assays. These studies revealed that both interleukin 1 alpha and interleukin 1 beta induced seven to tenfold increases in the levels of the third component. Similarly interferon alpha and interferon gamma stimulated an approximate four and ninefold dose-dependent increase, respectively, in the production of the third component. Analysis of the effect of interleukin 2 on third component production demonstrated that higher concentrations (100 U ml-1) were required to induce a fivefold increase in the production of the third component.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

Improved dose homogeneity in the breast using tissue compensators.

The improvements achievable by introducing individual tissue compensators in photon therapy of the breast were assessed. In 37 patients the dose ranged from +15% to -10% of the mid target dose using combinations of wedge filters and beam weights alone. With a tissue compensator the dose ranged from +4% to -11% provided that allowance was made for lung attenuation. A megavoltage imaging system is a potential source of the X-ray transmission data which can provide a basis for the calculation of thickness of the compensator.

Breast Neoplasms↗

What might echography learn from image science?

We review the current state of knowledge of the processes by which the information content of ultrasonic pulse-echo images is transferred to an observer, to the point of contributing to diagnostic judgments. As systematic knowledge in this specific field is rather sparse, we present relevant information and techniques derived from other areas of image science, both medical and otherwise. Quantitative measures both of the information content of ultrasonic and other images and of their characteristic noise content are first considered. An account is then given of the relevant aspects of human visual psychophysics, with particular reference to perception of contrast and detail, image texture, movement and colour, again with emphasis on documenting quantitative aspects of such behaviour. Against this background, we consider the efficiency, in current practice, of image information transfer to a human observer, how and to what extent this could be improved by changes in practice and, in particular, in what situations substantial innovations in machine processing of image data would be expected to improve human performance. It is suggested that several problems in the field may provide a worthwhile and challenging scope for future research.

Humans↗

An experimental model for the study of canine flexor tendon adhesions.

An experimental model for the study of canine flexor tendon adhesions was designed using a standardized crush-abrasion injury, meticulous sheath closure, and three-week limb immobilization. Ten animals in the experimental protocol were evaluated for visible adhesion formation. With use of a flexor tendon adhesion rating scale, consistent adhesion formation was documented with an average score of 10.4 +/- 2.1 (range, 0 to 12). Five additional animals had biomechanical testing. Applying an increasing load to the proximally divided profundus tendon (0 to 10 Newtons), it was found that the angle of distal interphalangeal joint motion and the displacement of the toe were significantly decreased, and the work generated significantly increased in the experimental versus control digits (p less than 0.05). The consistent production of visible adhesions thus correlates with biomechanical impairments in toe motion and work. The study of agents aimed at diminishing flexor tendon adhesions will thus be facilitated by this reliable model. Systemic or intrasheath administration of agents will be possible.

Animals↗

Optimization by simulated annealing of three-dimensional conformal treatment planning for radiation fields defined by a multileaf collimator.

Three-dimensional conformal radiotherapy may be achieved by using a combination of geometrically shaped radiation fields from different orientations around the patient. A convenient method to shape the fields is to use a multileaf collimator. These fields are shaped to the beam's-eye-view of the target volume, at each orientation of the collimator, and may also encompass sensitive structure, i.e. organs at risk, if the target region has concavities in its outline within which such structure may reside. The term 'conformal therapy' is used in this paper to mean tailoring the high dose volume to the target volume whilst minimising dose to other normal structures (organs at risk) which may be irradiated by the treatment fields, shaped by a multileaf collimator. The question then arises of the optimum distribution of beam weights to apply to the fields to minimise dose to organs at risk whilst aiming towards a uniform dose distribution in the target volume. This paper provides a method of optimizing the choice of beamweights to achieve this. The method is based on the well known optimization technique of simulated annealing. Either an optimal set of beamweights, one weight per field, is generated or the intensity may be spatially modulated across the field at each orientation (two weights per field) depending on whether there is just target volume or both target volume and volume containing organs at risk in the line of sight. It is shown that the dose matrix resulting from the latter optimization is closer to the dose prescription than that obtained by using either an optimal set of single weights per field or uniform beamweights.

Humans↗

Therapy begins at home: the psychiatric house call.

The house call is a valuable but underused component of community psychiatric care. A review of home visits conducted by the staff of a community mental health service over a 12 month period identified four situations in which a home visit is useful: getting reluctant patients to enter therapy, conducting a comprehensive assessment, strengthening a support network, and maintaining patients in the community when their condition has deteriorated. Making psychiatric house calls requires some additional skills on the part of therapists and offers residents valuable training experience.

Aged↗

Results of a province-wide quality assurance program assessing the accuracy of cholesterol, triglycerides, and high-density lipoprotein cholesterol measurements and calculated low-density lipoprotein cholesterol in Ontario, using fresh human serum.

To evaluate laboratory performance, eight to 13 samples of fresh human serum from volunteers were sent to 250 laboratories in the Canadian province of Ontario licensed to perform lipid analysis. Fresh human specimens were used because of potential matrix effects with processed materials. We show that on all survey samples, 71% (range, 63% to 82%) of participating laboratories are within +/- 5% of the target cholesterol value and that 93% are within +/- 10%. The goal of the National Cholesterol Education Program for 1992 is total error of no more than +/- 9% for 95% of results. The unblanked triglycerides results show that on all samples 40% (14% to 59%) of participants are within +/- 5% and 68% (range, 31% to 86%) are within +/- 10% of the target value. For triglycerides results from 0.9 to 2.0 mmol/L, 80% or more are within +/- 0.2 mmol/L. Between 2.0 and 3.0 mmol/L, 90% are within +/- 0.3 mmol/L of the target values. For high-density lipoprotein cholesterol, for all samples 35% (range, 24% to 50%) of laboratories are within +/- 5% and 68% (range, 55% to 88%) are within +/- 10%. A range of 80% to 95% of participants are within +/- 0.2 mmol/L of the target values. For calculated low-density lipoprotein cholesterol, 51% and 62% of the laboratories surveyed are within +/- 5%, with 83% and 89% within +/- 10% of the target values. We conclude that the laboratory measurement of lipids is approaching the degree of accuracy and precision required for clinical purposes, and that the use of fresh human serum samples is a viable approach to their proficiency testing.

Blood Chemical Analysis↗

Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.

The mechanism by which T lymphocytes are tolerized to self or foreign antigens is still controversial. Clonal deletion is the major mechanism of tolerance for immature thymocytes; for mature T cells, tolerance is considered to reflect anergy rather than deletion, and to be a consequence of defective presentation of antigen. This paper documents a novel form of tolerance resulting when mature T cells encounter antigen in immunogenic form. Evidence is presented that exposure of mature T cells to Mlsa antigens in vivo leads to specific tolerance and disappearance of Mlsa-reactive V beta 6+ T cells. Surprisingly, the clonal elimination of V beta 6+ cells is preceded by marked expansion of these cells. Thus, tolerance induction can be the end result of a powerful immune response. These data raise important questions concerning the relationship of tolerance and memory.

Animals↗

Cranial thickening in an Australian hominid as a possible palaeoepidemiological indicator.

This paper describes the cranial thickening of a late Pleistocene hominid (Willandra Lakes Hominid 50) from Australia. The unusual development of the vault structures in this individual has few, if any, equals among other hominids or more recent populations from around the world. The vault morphology is, therefore, described in terms of a pathologically related condition associated with the modern haemolytic blood dyscrasias, typical of sickle cell anamia and thalassemia. A possible palaeoepidemiology for these genetic adaptations among early Australasian populations is proposed together with a discussion of similar changes observed in the vault of the Singa calvarium from the Sudan. It is tentatively suggested that the cranial thickening of the Australian hominid has its origins in some form of genetic blood disease and that if this diagnosis is correct, this individual provides a rare glimpse of human biological adaptation in the late Upper Pleistocene.

Animals↗

Expression of hemochromatosis in homozygous subjects. Implications for early diagnosis and prevention.

This study looks at expression of genetic hemochromatosis in the homozygous and heterozygous states. Two hundred nine subjects in 40 families with confirmed hemochromatosis and clear evidence of HLA linkage in symptomatic individuals were studied prospectively for up to 24 yr. The study group consisted of 40 probands, 51 subjects sharing two HLA haplotypes with affected relatives (putative homozygotes), 98 putative heterozygotes, and 20 putative normal homozygotes. Forty-eight of 51 subjects predicted to be homozygous showed increased hepatic iron stores as assessed by liver biopsy and quantitative phlebotomy. If not evident initially, this developed in 1-8 yr. In the 3 subjects predicted by HLA typing to be homozygous but in whom there was no progressive iron accumulation, results of studies using another chromosome 6 genetic marker (Factor 13 A subunit) were consistent with chromosomal recombination, presumably separating one hemochromatosis allele from the HLA markers. No heterozygous subject developed overt hemochromatosis during the period of follow-up, although 1 showed evidence of iron overload at initial assessment. Genetic recombination is again thought to have separated the hemochromatosis allele from the HLA markers here. The present findings favor a location of the hemochromatosis locus telomeric to HLA-A. It is concluded that, in this population, hemochromatosis is apparently always HLA linked, and homozygous subjects will develop iron overload in the absence of chromosomal recombination or blood loss.

Adolescent↗

Non-standard CT scanners: their role in radiotherapy.

In the past 10 years a number of groups worldwide have investigated the extent to which the imaging requirements for radiotherapy planning may be met by the development of non-standard computed tomography (CT) scanners. Some of these groups have constructed apparatus based on a radiotherapy simulator gantry, others around a linac or a special purpose gantry. The performance of these systems is reviewed and the extent to which they have justified their promise has been assessed. The major use of simulator-based machines has been in planning radio-therapy in the thorax where tissue inhomogeneity corrections are important. Linac-based machines yield images useful for checking the positioning of patients at the time of therapy. Interest at the Royal Marsden Hospital culminated in the construction of a simulator-based CT system which achieved its present form in late 1985. The importance of the subsequent clinical study lies in our conclusive evidence that planning conservative radiotherapy for the breast without multiple-level CT performed in the treatment position can have implications for local control of disease, pulmonary damage, and cosmesis.

Animals↗

Three-dimensional x-ray microtomography for medical and biological applications.

Three-dimensional (3D) x-ray microtomography is a technique for obtaining the 3D distribution of x-ray attenuation coefficients within small objects. To obtain microtomographic images apparatus has been developed which consists of a microfocal x-ray source, a computer-controlled stage for rotating the object, a 2D multi-wire gas proportional x-ray counter and a microcomputer to control image acquisition. Projection data were generated by rotating the object to discrete orientations around a single axis until of the order of 100 2D projection images of the object were collected. The projection images were transferred to a VAX 11/750 computer for subsequent 3D reconstruction using a convolution and back-projection algorithm in cone-beam geometry. The reconstructed data, comprising cubic voxels, may be displayed as sets of sequential transaxial, sagittal and coronal planes through the object. Alternatively, perspective displays of individual orthogonal sections may be formed with either intersecting planes or with these planes projected onto the surfaces of a box-like structure. The technique provides for the investigation of small-scale structures in biological specimens and we show some illustrative images of dead insects.

Animals↗

Analysis of HLA-DQB and HLA-DPB alleles in Graves' disease by oligonucleotide probing of enzymatically amplified DNA.

We have tested the possible association of HLA-DQB and HLA-DPB alleles with Graves' thyrotoxicosis, with or without severe ophthalmopathy, by polymerase chain amplification of genomic DNA and allele-specific oligonucleotide probing. There was no significantly abnormal distribution of DQB alleles compared to 50 control subjects except for a reduced prevalence of DQw 3.1 in the Graves' patients with severe ophthalmopathy (X2 = 6.23, P less than 0.02). HLA-DPB 2.1/8 was found in only 1 of 40 of these patients compared with 15 of the controls (X2 = 11.49, P less than 0.001). Ten of 48 patients with Graves' disease but without clinically significant eye involvement were HLA-DPB 2.1/8 positive, not significantly different from controls, but significantly different from the ophthalmopathy group (X2 = 6.70, P less than 0.01). The other DPB alleles in both groups of Graves' disease patients were the same as controls. These results suggest that HLA-DPB 2.1/8 may confer a protective effect in Graves' disease with respect to ophthalmopathy.

Alleles↗

Postimplantation development of tetraploid mouse embryos produced by electrofusion.

Despite the fact that a variety of experimental techniques have been devised over the years to induce tetraploid mammalian embryonic development, success rates to date have been limited. Apart from the early study by Snow, who obtained development to term of a limited number of cytochalasin B-induced tetraploid mouse embryos, no other researchers have achieved development of tetraploid embryos beyond the early postimplantation period. We now report advanced postimplantation development of tetraploid mouse embryos following electrofusion of blastomeres at the 2-cell stage, and subsequent transfer of these 1-cell 'fused' embryos to appropriate recipients. Cytogenetic analysis of the extraembryonic membranes of all of the postimplantation embryos encountered in the present study has provided an unequivocal means of confirming their tetraploid chromosome constitution. A preliminary morphological and histological analysis of the tetraploid embryos obtained by this technique has revealed that characteristic craniofacial abnormalities particularly involving the forebrain and eyes were consistently observed, and these features were often associated with abnormalities of the vertebral axis and heart. The most advanced viable embryo in this series was recovered on the 15th day of gestation, and its morphological features suggest that it was developmentally equivalent to a normal embryo of about 13.5-14 days p.c.

Animals↗

Proficiency testing for creatine kinase isoenzyme CK-2 (CK-MB) in Ontario.

Three surveys of the measurement and interpretation of creatine kinase (CK; EC 2.7.3.2) isoenzyme 2 (CK-MB) were conducted in Ontario, Canada, in 1989. Of the clinical laboratories participating, 66% used immunological methods and 24% used electrophoretic methods. Although reference ranges and interpretative routines varied widely, 95% of the laboratories reported correct interpretations for 10 of the 15 vials tested. The only major problems occurred with samples with very low total CK activity. Within-survey duplicate results compared well, and 89% of the laboratories had consistent between-survey results, even for specimens with low total CK activity. Errors were proportional to the frequency of use of the different analytical methods. The lyophilized testing material gave higher results with methods for measuring the mass of CK-2, suggesting that the material contained inactive but immunologically intact CK-2. The surveys indicate that laboratories should review their protocols for measuring CK-2 when only a single sample from the patient is available.

Creatine Kinase↗