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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 73 records · Page 4Linked to original sources
PubMed1999

Analysis of leucocyte subsets in the canine intestine.

Immunohistochemistry and computer-aided morphometric analysis were used to define populations of leucocyte subsets in the intestinal tract of an outbred population of dogs with no evidence of gastrointestinal disease. In the small intestinal lamina propria, B cells and plasma cells (IgA+, IgM+ and IgG+) were prominent in peri-crypt regions, with a significant trend for a reduction in the number of cells towards the villous tip (P < 0.0001). By contrast, lamina propria T cells (CD3+) and T-cell subsets (CD4+ and CD8+) were present in greatest numbers at the tip of the villus, with significantly decreasing numbers towards the crypt regions (P < 0.0001). In the lamina propria, CD4+ cells outnumbered CD8+ cells (P = 0.05), but the opposite was true of the epithelial compartment (P < 0.001). The distribution of CD5+ lymphocytes was similar to that of CD3+ cells, in both the lamina propria and epithelial compartments. The numbers and distribution of cells expressing MHC class II, L1 and CD45 were recorded. Numerous eosinophils were present in the lamina propria, and an intra-epithelial population was also noted, especially in the crypt epithelium. Mast cells, which were mainly found in the subepithelial lamina propria, were also present within muscle layers, and cells expressing IgE had a similar distribution. Similar populations of cells were recorded in the colonic lamina propria and epithelium. The quantitative and qualitative data from this study will enable comparisons to be made with dogs suffering from inflammatory bowel diseases.

Age Factors↗
PubMed1999

The distribution of lymphocytes expressing alphabeta and gammadelta T-cell receptors, and the expression of mucosal addressin cell adhesion molecule-1 in the canine intestine.

The present study defined the distribution of alphabeta and gammadelta T-cell subsets, and the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the intestinal tract of an outbred population of dogs with no evidence of gastrointestinal disease. A panel of monoclonal antibodies reactive with the canine alphabeta and gammadelta T-cell receptors (TCRs) and human MAdCAM-1 was used in a series of immunoperoxidase or immunofluorescence studies. alphabeta T cells were predominant within the villous lamina propria with a significantly decreasing linear trend from upper villus to crypt (P<0.0001). A proportion of intraepithelial lymphocytes (IELs) also expressed the alphabeta T-cell receptor, with significantly greater numbers in villous than in crypt epithelium (P<0.0001). However, there were no significant differences in the numbers of either lamina propria or epithelial alphabeta T cells between different intestinal regions. gammadelta T cells were rare in the lamina propria, but a prominent gammadelta IEL population was present and shown by double-colour immunofluorescence studies to be principally of the CD4(&)minus;CD8alpha(&)minus; phenotype. MAdCAM-1 was expressed by endothelial cells in the mucosa, sub-mucosa and muscularis layers of all levels of the intestinal tract. In the mucosa, significantly more MAdCAM-1 positive endothelium was present in regions of crypt than villous lamina propria (P<0.0001), but there were no significant differences between expression in different intestinal regions. The quantitative and qualitative data will enable comparisons of these parameters to be made with those in dogs suffering from inflammatory bowel diseases.

Animals↗
PubMed1999

Neutron-energy-dependent cell survival and oncogenic transformation.

Both cell lethality and neoplastic transformation were assessed for C3H10T1/2 cells exposed to neutrons with energies from 0.040 to 13.7 MeV. Monoenergetic neutrons with energies from 0.23 to 13.7 MeV and two neutron energy spectra with average energies of 0.040 and 0.070 MeV were produced with a Van de Graaff accelerator at the Radiological Research Accelerator Facility (RARAF) in the Center for Radiological Research of Columbia University. For determination of relative biological effectiveness (RBE), cells were exposed to 250 kVp X rays. With exposures to 250 kVp X rays, both cell survival and radiation-induced oncogenic transformation were curvilinear. Irradiation of cells with neutrons at all energies resulted in linear responses as a function of dose for both biological endpoints. Results indicate a complex relationship between RBEm and neutron energy. For both survival and transformation, RBEm was greatest for cells exposed to 0.35 MeV neutrons. RBEm was significantly less at energies above or below 0.35 MeV. These results are consistent with microdosimetric expectation. These results are also compatible with current assessments of neutron radiation weighting factors for radiation protection purposes. Based on calculations of dose-averaged LET, 0.35 MeV neutrons have the greatest LET and therefore would be expected to be more biologically effective than neutrons of greater or lesser energies.

Animals↗
PubMed1999

Clinical laboratory evaluation of small intestinal function.

Although diarrhea as a consequence of dysfunction of the small intestine (SI) is a common presenting problem in practice, most cases are acute, nonfatal, and self-limiting, and they require only symptomatic support. Thus, the need for any investigation of SI function beyond physical examination is a clinical judgment made on the potential of the problem being persistent, contagious, or life-threatening. Acute, severe, or bloody diarrhea; concurrent signs of systemic illness; or chronic diarrhea (which is not self-limiting) indicate a need for more detailed investigations. In all cases, the fluid and electrolyte needs of the patient must be addressed even while the diagnostic effort is in progress.

Animals↗
PubMed1998

Measurement of IgG, IgM and IgA concentrations in canine serum, saliva, tears and bile.

Capture ELISAs, for canine IgG, IgM, IgA and albumin, were developed and used to analyse immunoglobulin (Ig) concentrations in both serum and secretions. Matched samples of serum, saliva and tears were taken from 31 dogs, assigned to two groups based on age, whilst bile samples were obtained from nine adult dogs at post-mortem. Serum and tear IgA concentrations were significantly lower in dogs < or = 12 months of age compared with dogs > 12 months of age (p = 0.006 and 0.045, respectively). There was no significant correlation between serum and secretory Ig levels, with the single exception of serum and tear IgM concentrations (rp = 0.553, p = 0.004). IgG and IgM concentrations were significantly correlated in matched tear and saliva samples (IgG: rp = 0.470, p = 0.023; IgM: rp = 0.651, p < 0.0001). Albumin concentrations were significantly correlated with IgG, but not IgM or IgA, in both saliva and tears (saliva, rp = 0.581, p = 0.004; tears, rp = 0.843, p < 0.0001) whilst IgA and IgM concentrations were significantly correlated with each other in both secretions (saliva, rp = 0.644, p = 0.001; tears, rp = 0.555, p = 0.009). Significantly, more Ig of all classes was secreted into saliva than tears as calculated by a secretory index. A large diurnal and day-to-day variation was observed in Ig concentrations in serial saliva and tear samples taken from a further four dogs. Serum Ig concentrations are therefore, poor indicators of mucosal secretion in this species and significant intra-individual variation exists in secretory Ig levels. Both findings should be taken into account in future studies of canine mucosal immunoglobulins.

Animals↗
PubMed1998

Expression of major histocompatibility complex class II antigens in the canine intestine.

Immunohistochemical techniques were used to assess major histocompatibility complex (MHC) class II expression by enterocytes and lamina propria cells in the canine intestinal tract. Duodenal enterocyte class II expression was faint and limited to the lower crypt region whereas jejunal and ileal enterocyte expression was stronger, being present in both crypt and villus areas. Enterocyte staining was of greatest intensity in crypts adjacent to Peyer's patches and intense membrane staining of most Peyer's patch lymphocytes was also seen. Enterocyte MHC class II expression in the colon was largely limited to the lower crypt region. Within the lamina propria, of all intestinal sites examined, a heterogeneous population of cells were MHC class II positive and these had morphological features of macrophages and dendritic cells. Lymphocytes, plasma cells, fibroblasts and vascular endothelium were not stained. Definition of constitutive expression of MHC class II within the canine intestine may be important in identifying upregulation of this molecule in inflammatory bowel diseases.

Animals↗
PubMed1998

Genomic instability and tumorigenic induction in immortalized human bronchial epithelial cells by heavy ions.

Carcinogenesis is postulated to be a progressive multistage process characterized by an increase in genomic instability and clonal selection with each mutational event endowing a selective growth advantage. Genomic instability as manifested by the amplification of specific gene fragments is common among tumor and transformed cells. In the present study, immortalized human bronchial (BEP2D) cells were irradiated with graded doses of either 1GeV/nucleon 56Fe ions or 150 keV/micrometer alpha particles. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Tumorigenic cells showed neither ras mutations nor deletion in the p16 tumor suppressor gene. In contrast, they harbored mutations in the p53 gene and over-expressed cyclin D1. Genomic instability among transformed cells at various stage of the carcinogenic process was examined based on frequencies of PALA resistance. Incidence of genomic instability was highest among established tumor cell lines relative to transformed, non-tumorigenic and control cell lines. Treatment of BEP2D cells with a 4 mM dose of the aminothiol WR-1065 significantly reduced their neoplastic transforming response to 56Fe particles. This model provides an opportunity to study the cellular and molecular mechanisms involved in malignant transformation of human epithelial cells by heavy ions.

Alpha Particles↗
PubMed1998

Effect of track structure and radioprotectors on the induction of oncogenic transformation in murine fibroblasts by heavy ions.

The oncogenic potential of high-energy 56Fe particles (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at the Brookhaven National Laboratory was examined utilizing the mouse C3H 10T1/2 cell model. The dose-averaged LET for high-energy 56Fe is estimated to be 143 keV/micrometer with the exposure conditions used in this study. For 56Fe ions, the maximum relative biological effectiveness (RBEmax) values for cell survival and oncogenic transformation were 7.71 and 16.5 respectively. Compared to 150 keV/micrometer 4He nuclei, high-energy 56Fe nuclei were significantly less effective in cell killing and oncogenic induction. The prostaglandin E1 analog misoprostol, an effective oncoprotector of C3H 10T1/2 cells exposed to X rays, was evaluated for its potential as a radioprotector of oncogenic transformation with high-energy 56Fe. Exposure of cells to misoprostol did not alter 56Fe cytotoxicity or the rate of 56Fe-induced oncogenic transformation.

Animals↗
PubMed1998

From chimney sweeps to astronauts: cancer risks in the work place: the 1998 Lauriston Taylor lecture.

Percival Pott, in 1775, was the first to note an association between overt cancer and a carcinogen in the work place when he astutely observed an elevated incidence of scrotal cancer in small boys who assisted chimney sweeps. In their "workplace" astronauts and crew of high altitude jet-liners are exposed, not only to low linear energy transfer (LET) radiation but also to HZE (high energy + high atomic number) particles and to neutrons-for which no human epidemiological data exist. The current system of radiation protection is based on risk estimates from low LET radiations, delivered in large doses and at high dose-rate, coupled with the assumption of a linear no-threshold model. In extrapolating to low doses and dose-rates, and to high LET radiations, it would be helpful if the mechanisms of radiation carcinogenesis were known. Unfortunately that is not the case, though progress has been made toward that end. Many human leukemias and lymphomas appear to be due to specific chromosomal translocations, while solid tumors usually involve multiple mutations in oncogenes, deletions in suppressor genes, and/or chromosomal rearrangements. Genomic instability and immortality are hallmarks of cancer and it is attractive to hypothesize that this is due to a mutation in a gene or genes responsible for the stability of the genome. Examples abound of a small DNA change inactivating a gene and leading to major biological consequences. This could result from a single particle, especially a HZE particle, or a recoil proton from the absorption of a neutron. In this context the assumption of a threshold is hazardous, and the linear no-threshold hypothesis still appears to be prudent and conservative.

Astronauts↗
PubMed1997

Pulsed-dose-rate brachytherapy: design of convenient (daytime-only) schedules.

PURPOSE: To design pulsed-brachytherapy (PDR) protocols that are expected to be at least as clinically efficacious (in terms of both tumor control and late sequelae) as continuous low-dose-rate (CLDR) regimens, but that involve irradiation only during extended office hours. Both interstitial and intracavitary brachytherapy protocols are considered. METHODS AND MATERIALS: The linear quadratic formalism was used in which the late normal tissue damage and tumor control for one protocol relative to another are assumed to be determined primarily by the level of cellular survival. PDR schedules were designed in which pulses are delivered during "extended office hours" (8 A.M. to 8 P.M.) with no irradiation overnight. Generally, the proposed PDR regimes last the same number of treatment days as the corresponding CLDR regimen, but the PDR treatment lasts longer on the final day (i.e., until 8 P.M.). PDR doses were calculated such as to produce a tumor control which is equivalent to standard CLDR protocols, and the corresponding predicted late complication rate was compared with that for CLDR. Ranges of plausible values for the half-times of sublethal damage repair for tumors and for late-responding normal tissues were considered. RESULTS: As has been previously shown, the efficacy of PDR relative to CLDR depends considerably on the repair rates for sublethal damage repair. Clinical and experimental evidence suggests that average repair half-times for early effects (e.g., tumor control) are less than about a half hour, and for late sequelae are more than about an hour. If these estimates are correct, daytime PDR regimes can usually be designed which take the same number of days as the corresponding CLDR regimen, but have comparable or better therapeutic ratios than CLDR. CONCLUSION: Protocols for PDR can be designed to involve irradiation only during extended office hours, that are likely to result in clinical results comparable or better than CLDR, for any expected combination of the repair half-times of early- and late-responding tissues. The suggested protocols allow all of the advantages of a computerized remote-controlled afterloader while preserving the benefits of low dose rate. In addition, the protocols could allow the patient to go home overnight, or to stay overnight in an adjacent medical inn or hospital-associated hotel, rather than in a hospital bed-which could have major economic benefits. In such an economic situation, an extra treatment day for the daytime PDR could well be considered, which would virtually guarantee an improved clinical advantage relative to CLDR.

Brachytherapy↗
PubMed1997

Pulsed brachytherapy as a substitute for continuous low dose rate: an in vitro study with human carcinoma cells.

PURPOSE: Pulsed dose rate (PDR) brachytherapy as a substitute for continuous low dose rate (CLDR) has the potential to be a useful option in brachytherapy. However, the frequency and duration of pulses that will produce results practically equivalent to CLDR is still an open and important question. This study was designed to compare the survival of human tumor cells, cultured in vitro, and exposed to continuous or pulsed irradiation where the pulse frequency was varied. METHODS AND MATERIALS: Three different human carcinoma cells, derived from cervical and breast cancers, were exposed to CLDR gamma rays, or to pulsed irradiations with the same overall dose rate. Pulsed regimens used were 3.8 min every hour, 7.6 min every 2 h, 11.4 min every 3 h, 15.2 min every 4 h, 22.8 min every 6 h, and 45.6 min every 12 h. For each comparison between CLDR and PDR, the overall dose and the overall time were the same. Experimental design was such that significant differences in biological effectiveness, if present, would be detected. RESULTS: For the cell lines investigated, hourly pulses resulted in cell survival indistinguishable from CLDR. However, as the pulse interval was increased, cell survival progressively decreased compared with CLDR, and the pulsed regimes were no longer equivalent to continuous low dose rate. CONCLUSIONS: This study provides some evidence to support the suggestion that a 10-min pulse, repeated every 1 to 2 h, would be functionally equivalent to a continuous low dose rate irradiation, at least in terms of early responding endpoints. Longer intervals between pulses might result in loss of equivalence in some cases.

Brachytherapy↗
PubMed1997

Contrast sensitivity in infants and children with Down syndrome.

A new contrast sensitivity (CS) card test was used to estimate contrast sensitivity in 18 infants and children with Down syndrome (DS). The results showed that although the overall shape of the contrast sensitivity functions (CSFs) of the subjects with DS was the typical inverted-U, their CSFs were depressed in comparison to control subjects and this relative loss became larger with increasing spatial frequency. In addition, there was little improvement in CS with age and the mean CSF among children with DS (mean age = 7.3 years) was equivalent statistically to a group of 12-month-olds without DS. The Teller Acuity Cards (TAC) were also used to assess visual acuity in 17 of the 18 children in our sample. The results of these tests showed that their visual acuity (VA) was significantly lower than normal, but was consistent with that extrapolated from each subject's CSF. Taken together with previous anatomical and developmental findings, our results suggest that the deficits in spatial vision among children with DS is due primarily to restricted cortical development, and secondarily, to the additional accommodative and ocular conditions that are prevalent in this population.

Adolescent↗
PubMed1997

What will molecular biology contribute to our understanding of radiation-induced cell killing and carcinogenesis?

The vast body of radiobiological data accumulated with mammalian systems in vitro and in vivo has had an enormous impact on radiotherapy. However, while quantitative, these data are essentially phenomenological, and it is only in the last decade or so that the techniques of molecular biology allow basic mechanisms to be understood. This will be illustrated by two examples, one involving cell killing and the other carcinogenesis. The identification and sequencing of repair and checkpoint control genes in the yeast S. pombe allow the mechanism of sensitivity/ resistance to radiation to be understood at the molecular level. The development of techniques to identify mutations in mismatch repair genes have made it possible to show that such mutations are associated with a wide range of human cancers and are a likely mechanism of radiation induced malignancies. Tikvah Alper would have been delighted to see the central role that micro-organisms have played in these recent developments.

Amino Acid Sequence↗
PubMed1996

The radiobiology of intravascular irradiation.

PURPOSE: There is increasing interest in the use of vascular irradiation, from an internally introduced radioactive source to control restenosis after balloon angioplasty. Both animal experiments and early clinical studies appear to show promising results in this regard. We consider various mechanistic interpretations of the experimental and clinical observations that doses of 12-20 Gy appear to be efficacious in preventing restenosis. We develop and investigate simple models, both experimental and theoretical, of the kinetics of radiation-induced smooth muscle cell (SMC) inactivation and regrowth, as a first step toward optimizing the design of clinical vascular irradiation. METHODS AND MATERIALS: Using in vitro models of human SMCs, we investigate the relative radiosensitivity of SMCs compared with endothelial cells and measure the dose-dependent ability of SMCs to repopulate a denuded region in a confluent layer of cells. We then use quantitative information on the number, radiation sensitivity, and growth rate of the potential arterial target cells to model the time course of the SMC population after irradiation. RESULTS AND CONCLUSION: Doses >20 Gy, which would be required to completely eliminate the SMC population which has the potential to cause restenosis, are too large to be practical because of the unacceptable risk of late complications. However, doses that can be practically given in vascular irradiation (<20 Gy) will certainly delay restenosis by 1-3 years, with larger doses producing longer delays. Whether such doses can avert restenosis permanently is unclear, as permanent prevention at realistic doses depends critically on the assumption that those SMCs which survive irradiation have a significantly limited capacity for proliferation. With regard to current animal model experiments, routine follow-up of <1 year, which is standard practice, is probably too short to address some of the key mechanistic question in intravascular radiation therapy.

Angioplasty, Balloon, Coronary↗
PubMed1996

Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny.

Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus that telomere length is stabilized by the activity of telomerase in immortal cells; however, it is not clear why some immortal cells display chromosome end-to-end associations. In the present study we evaluated chromosome end-to-end associations, telomere length and telomerase activity with the tumorigenic status of human bronchial epithelial cells immortalized with human papillomavirus. Oncogenic transformation was initiated using radon simulated alpha-particles and cells evaluated as primary, secondary and metastatic transformants. The fewest chromosome end associations and lowest telomerase activity were observed in the parental immortalized cells. However, increased levels of telomerase activity were detected in alpha-particle survivors while robust telomerase activity was seen in the tumorigenic cell lines. The tumorigenic cells that were telomerase positive and had the highest frequency of cells with chromosome end-to-end associations were also metastatic. No correlation was found between telomere length and the different stages of carcinogenicity.

Ataxia Telangiectasia↗
PubMed1996

Quantitative comparisons of continuous and pulsed low dose rate regimens in a model late-effect system.

PURPOSE: There is increasing interest and usage of pulsed low dose rate (PDR) brachytherapy, in which a single source is shuttled through the catheters of an implant, typically for about 10 min each hour. This study was designed to compare the late effects produced in various PDR regimens with those from the corresponding continuous low dose rate (CLDR) regimens. METHODS AND MATERIALS: A model late-responding system was used, namely, cataract induction in the rat lens. This system has the advantage of being highly quantifiable. The rats eyes were exposed to a total dose of 15 Gy either continuously over 24 h, or with three different PDR regimens, all with the same total dose and overall time. We addressed three questions: (a) are late effects increased when a CLDR regimen is replaced with 10-min pulses repeated every hour? (b) Are late effects increased if hourly 10-min pulses are replaced with 10-min pulses repeated every 4 h? (c) Are late effects increased if 10-min pulses are replaced with 100-s pulses? RESULTS: We found that the four regimens under test, continuous, 10-min pulses each hour, 10-min pulses every 4 h, and 100-s pulses every hour, showed no significant differences in cataractogenic potential, as estimated with the Wilcoxon-Gehan test. Power tests indicated that the experimental design was adequate to detect relatively small differences in cataractogenicity between regimens. CONCLUSIONS: The equality of late effects from CLDR and PDR in these experiments must imply that sublethal damage repair is quite slow in this model late-responding system, in agreement with trends observed in the clinic for sublethal damage repair of late sequelae. Such trends would suggest that PDR is unlikely to produce significantly worse late effects than the corresponding CLDR regimen, which is in agreement with early clinical data using PDR. Caution, however, is strongly recommended.

Animals↗