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S A Roberts

Publications and source records attributed to S A Roberts.

At least 163 records · Page 9Linked to original sources
PubMed1992

Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine.

In vivo bromodeoxyuridine (BrdUrd) labelling of the human large bowel was performed and a detailed histochemical localisation of label in sections of crypts was undertaken using a monoclonal antibody to BrdUrd containing DNA. Flow cytometric studies on extracted nuclei were also performed (data presented elsewhere). The average crypt in the human large bowel (excluding the rectum) was 82 cells in height and 41 cells in circumference, with a total of about 2000 cells (assuming a topographical correction factor of 0.6). Ten per cent of the cells were replicating their DNA--that is, were in the S phase of the cell cycle--and 0.4% were in mitosis. The median position for the labelling index versus cell position frequency plot is at the 20th cell position--at a quarter of the crypt height. The lower and upper limits of the cell proliferation are given by the 5th and 95th percentiles at cell positions 4 and 43 respectively. The peak labelling index is about 30% and it occurs at cell position 15. The labelling index at the crypt base, the probable stem cell zone, is about 14%, suggesting that these cells have a longer cell cycle. Taking a value of 8.6 hours for the duration of the S phase (deduced from the flow cytometric data) and assuming a growth fraction of 1.0 for the mid-crypt, these data provide an estimate of about 30 hours for the cell cycle time. The rectal crypts are about the same size but contain about 30% fewer S phase cells. The data also yielded a per cent BrdUrd labelled mitosis curve.

Aged↗
PubMed1992

Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli.

The distribution of DNA synthesising cells in the crypts of the epithelium in human small and large bowel after injection of bromodeoxyuridine into patients has been studied in relation to the position of the cells in the crypt using immunohistochemistry. Different sites of normal epithelium have been studied. The ileum has a shorter crypt and a very significantly smaller total cell population size. However, it has similar peak labelling index (LI) values to the colon, while the rectum has a lower peak LI value. The mean position of the label occurs at the 17th cell position in the ileum and at about the 22nd position in both the colon and rectum. The overall mean LI is significantly higher in the ileum at 17.8%, intermediate in the colon at 10.3%, and lowest in the rectum at 8.5%. There is thus an inverse relation between the likelihood of developing a tumour and the rate of cell proliferation as measured by the LI. Assuming a value of 8.6 hours for the duration of S, the data suggest that the cell cycle time in the mid crypt region is about 30 hours for the ileum and colon and about 37 hours for the rectum. Samples taken adjacent (within 1 cm) to a tumour show a general dampening of proliferative activity at all cell positions compared with samples taken more than 5 cm from a tumour. This is illustrated by the average LI, which is about 5.4% in the colon adjacent to a tumour compared with 10% distant; comparable values for the rectum are 4.6% and 8.5%. Samples taken from two patients with polyposis coli show distributions with a significant difference in skewness compared with normal colon and a general shifting of the distribution to the right, that is to higher cell positions. There is a significant increase in the mean cell position and the position of the peak LI in the polyposis coli samples.

Adenomatous Polyposis Coli↗
PubMed1992

The clonogen content of murine intestinal crypts: dependence on radiation dose used in its determination.

The number of colony-forming (clonogenic) cells in each of the crypts in mouse small intestine was deduced using a two-dose irradiation technique. The number was 7.5 +/- 0.8 cells using two equal doses each less than 9 Gy and 38 +/- 7 cells using 9 Gy or more per dose. The significant dose dependence could not be accounted for by considerations of intra- or intercrypt variability, or by the factor introduced to correct the sampling frequency for the influence of crypt size. The results suggest that more colony-forming cells may be recruited when the injury is more severe.

Animals↗
PubMed1991

Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast.

The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.

Adolescent↗
PubMed1991

Changes in the hormone dependency of epithelial cell proliferation in the genital tract of mice following neonatal oestrogen treatment.

The genital tract epithelium of the female laboratory mouse has been widely studied as a model of oestrogen-dependent growth and proliferation. Perturbation of the hormonal imprinting of these tissues during neonatal development has also been used to study the development of pathological abnormalities, particularly in the cervical epithelium. This study demonstrates that mice treated neonatally from days 1-5 with supraphysiological concentrations of oestrogen are able to maintain high levels of proliferation following the removal of the ovaries later in adult life. This high level of proliferation was shown to be independent of the ovarian oestrogens and of oestrogens produced peripherally by aromatisation. These results suggest conversion of the genital tract in these mice to a fully hormonal "independent" state. However, neonatal treatment with oestrogen was not found to produce a uniform change to hormonal independence. Further challenge of the adult ovariectomised mice with oestrogen, demonstrated that a population of cells still retained the ability to respond to the mitogenic influence of this hormone.

Animals↗
PubMed1991

The sensitivity of human tissues to changes in dose fractionation: deductions from the RCR survey among UK radiotherapists.

The dosage prescriptions reported in the Royal College of Radiologists' fractionation survey among radiotherapists have been further analysed using model equations in order to deduce estimates of fractionation-sensitivity parameters for each of the six cases under consideration. For example, using the linear-quadratic model, including a (significant) time factor, with radical treatments of a T2 breast carcinoma or a T1N0 squamous carcinoma of the vocal cord, the (alpha/beta) ratios were 26 +/- 20 Gy and 37 +/- 46 Gy, respectively. The values of the time factor, expressed as the maximum extra dose required per day to counteract the decrease in effect with increasing overall time (gamma/alpha), were 0.60 and 0.45 Gy/day respectively. Using the Ellis formula, which provided a significantly better fit to the dosage prescription (P = 0.003), the exponents of N were calculated to be 0.24 +/- 0.05 and 0.27 +/- 0.07, respectively. The corresponding values of the T exponent were 0.16 +/- 0.06 and 0.014 +/- 0.075. About 20% of radiotherapists prescribed doses greater than +/- 10% from the mean fitted values for the breast treatment, and about 6% of them in the case of the vocal cord.

Aged↗
PubMed1991

Results of speech perception and speech production training for three prelingually deaf patients using a multiple-electrode cochlear implant.

Five studies were conducted to measure changes in the perception and production of selected speech targets, with training, in three prelingually deaf patients. The two adults and one adolescent were implanted with the Cochlear (Nucleus) multiple-electrode prosthesis. The studies were perception and production of nasal consonants; perception of syllable-final consonants; perception and production of alveolar consonants; auditory-visual perception of alveolar consonants; and perception and production of vowels. Perceptual data were collected in the audition (implant)-alone condition, except for the auditory-visual perception of alveolar consonants where the audition-alone, vision-alone, and auditory-visual conditions were used. Speech perception data in the audition-alone condition were also collected from four postlingually deaf adult implant patients, without training, to indicate differences between the two classes of patients. The three prelingually deaf patients generally showed some improvements in speech production. In perception, improvements were recorded only for individual patients in some studies. The performance of the adolescent was better than that of the two adults in all cases. The perceptual performance of the postlingually deaf patients was superior to that of the prelingually deaf patients in all cases.

Adolescent↗
PubMed1990

Acetaminophen structure-toxicity studies: in vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide.

High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled [3H or 14C]3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of [G-3H]acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAA was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of [ring-3H]3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential.

Acetaminophen↗
PubMed1990

Radiosensitivity testing of primary cervical carcinoma: evaluation of intra- and inter-tumour heterogeneity.

Biopsies from 89 patients with cervical carcinoma were studied using a clonogenic assay to obtain values for the surviving fraction at 2 Gy (SF2). Heterogeneity in intrinsic radiosensitivity was investigated by independently processing multiple biopsies from 18 tumors. No significant differences between intra-tumour SF2 values were demonstrated (p = 0.30). The results have shown that intra-tumour heterogeneity is not a limitation to radiosensitivity testing using the Courtenay-Mills assay. A wide range of values (0.13-0.97) for SF2 was obtained with a mean value of 0.47 +/- 0.18 (+/- 1 S.D., CV = 38%) for 52 squamous cell carcinomas and 0.59 +/- 0.27 for four adenocarcinomas. There were statistically significant differences between the individual tumours (p less than 0.001). From the analysis-of-variance of all the SF2 results it appears to be the surviving fractions below about 0.40 and those above about 0.7 which show significant differences in radiosensitivity between pairs of tumours (p = 0.05). Also 36% of the values of SF2 show significant differences from the mean SF2 of all tumours. The storage of tumour cell suspensions in liquid nitrogen improved the colony-forming efficiency (CFE) but it did not alter the radiosensitivity.

Analysis of Variance↗
PubMed1990

The temporal and spatial changes in cell proliferation within the irradiated crypts of the murine small intestine.

The detailed temporal and spatial changes in the labelling index in crypts of the small intestine of the mouse have been analysed after 8.0 Gy gamma-irradiation. The labelling index was determined for each cell position in the crypts at 34 different times between 3 and 192 h after irradiation. The changes between consecutive time points have been analysed to determine the details of the crypt shrinkage and crypt repopulation phenomena. The following points can be made: (1) There is a dramatic reduction in the overall labelling of the crypt which begins within 3 h and is at its minimum by 15 h postirradiation. Most of this shrinkage can be attributed to continued near-normal emigration of cells from the crypt to the villus while mitosis is reduced or absent, and a possibly premature maturation within the transit population. (2) The labelling index never falls below 34 per cent of control, i.e. many labelled cells persist and continue to replicate their DNA at all times postirradiation. (3) Repopulation begins in the lower regions of the crypt. The first changes are an increase in labelling at cell positions 3-8 that begins at 3 h and reaches a peak at 12 h. There is a second increase in proliferation at the crypt base that begins at about 15 h and reaches a peak at 22-32 h postirradiation. There is a third peak which begins at about 46 h and reaches a peak at 60-70 h. (4) There is a reduction in proliferation at the crypt base that begins at about 72 h postirradiation. (5) The mid and upper crypt population shrinks initially to reach a minimum at about 15 h, after which there is a steady increase to reach a peak at about 72 h. The labelling spreads into the crypt-villus boundary area beginning at about 32 h. There is a reduction of proliferative activity in the mid-crypt region that begins at about 72 h. (6) There is a dramatic overshoot in overall labelling index at 72 h, which involves mainly the upper crypt. This does not revert to normal levels within the 192 h time scale of the present experiments. There is a mild overshoot in labelling at the crypt base at 48-78 h with a return to normal levels thereafter.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Proliferative changes in the genital tissue of female mice during the oestrous cycle.

Changes in proliferation and number of epithelial cells of the murine genital tract, during the oestrous cycle, have been studied. A total of 47 animals in the prooestrous, metoestrous and dioestrous phases of the cycle were staged retrospectively on the basis of the genital tract histology. The average duration of the oestrous cycle in these animals was 4 days, and half of this period was occupied by the prooestrous/oestrous phases. Significant cycles of growth were observed in the luminal uterine epithelium and in the basal epithelium of the cervix-vagina. Most of this growth occurred during the pro-oestrous phase, which lasted approximately 1 day. During this time the numbers of luminal epithelial cells in the uterus and suprabasal cells in the cervix-vagina increased 2-3 fold. This pattern of growth appeared partly synchronous and corresponded to the period when serum oestrogen levels are at their highest. A corresponding and rapid reduction in the numbers of uterine luminal epithelial cells and suprabasal cells in the cervix and vagina was noted during the early metoestrous phase; and this occured during the period when serum oestrogens are at their lowest levels. No significant periodicity in the proliferation and numbers of the uterine gland epithelial cells was noted during the cycle. The kinetic role and function of the gland cells is discussed in relation to these data.

Animals↗
PubMed1990

Cranial hemihypertrophy and neurodevelopmental prognosis.

Three cases of congenital cranial hemihypertrophy are described. CT or ultrasound scans showed unilateral cerebral enlargement with dilatation of the ipsilateral ventricle. Seizures occurred in two patients and the neurodevelopmental outlook appears poor. These patients represent a poor prognosis subgroup of the congenital hemihypertrophies.

Brain↗
PubMed1990

Analysis of dose-incidence relationships for marrow failure in different species, in terms of radiosensitivity of tissue-rescuing units.

The analysis of 68 published sets of dose-incidence data for marrow failure in different species, using a double-log mortality function, indicates: (a) There is more heterogeneity, i.e. greater sums-of-squares per degree of freedom, within the data sets for mouse than for larger species (monkey, dog, sheep, goat, pig). (b) For mice the curves for acute doses are characterized by a D0 of about 100 cGy for tissue-rescuing units (or target cells), which are depleted at most to about 3 x 10(-4) at LD50. (c) Larger species are much less tolerant to target-cell depletion, the corresponding level being consistently in the range of 10(-2)-10(-3) at LD50. Also, the D0 is often lower (approximately 55 cGy), which is compatible in the dog with such a value for hemopoietic progenitor cells. (d) With larger species there is an unexpected reduction in heterogeneity when the dose rate is lower, which gives a D0 lower than expected and a higher extrapolate. It is concluded that the position and slope of the dose-incidence curves are compatible with interpretations based primarily on target-cell number and survival characteristics, modified by additional heterogeneity factors.

Animals↗
PubMed1990

Post-mortem biochemistry of beagle dog lenses after treatment with Fluvastatin (Sandoz) for 2 years at different dose levels.

Post-mortem biochemical analyses of dog lenses and of aqueous humour of a 2 year oral toxicity study in the dog with Fluvastatin (control, 1, 8 and 16 mg/kg/day) did not show any relationship to the observed lens opacities (3 animals out of 8 at 16 mg/kg/day). With respect to lens transparency, a daily dosage of 8 mg/kg/day Fluvastatin to dogs over a period of 2 years is non-cataractogenic. Mean data on lenticular enzyme activities (GPX, G6PH, GAPDH, ALD, AR, LDH, PFK and SDH) as well as measurements of GSH/GSSG, ATP, ADP, AMP, Gluc, Fruc, Sorb, G6P and F6P do not indicate changes which may directly lead to lens opacifications. Conformational changes of lens proteins (heat lability of PFK-activity), a shift in the albumin/IgG ratio of aqueous humour and equatorial lens protein composition changes (after isoelectrofocusing) were observed. The biological significance of these changes is unknown as the non-cataractogenic dose for lens opacities in beagle dogs is 8 mg/kg/day.

Animals↗
PubMed1989

Bis(benzenethiolato)nitrosyl [tris(3,5-dimethyl-1-pyrazolyl)hydroborato]-molybdenum(II) .

[Mo(C15H22BN6)(C6H5S)2(NO)], Mr = 641.5, monoclinic, P2(1)/n, a = 10.898 (1), b = 18.484 (2), c = 15.989 (2) A, beta = 109.81 (1) degree, V = 3030.2 A3, Z = 4, Dx = 1.41, Dm = 1.41 g cm-3, lambda(Mo K alpha) = 0.7173 A, mu = 5.9 cm-1, F(000) = 1320, T = 293 K, wR = 0.047 for 3997 observed reflections. In each complex, the Mo atom is six-coordinate, ligated by a terminal NO group, a tridentate pyrazolylborate ligand and two benzenethiolate ligands. The structure is compared with that of similar complexes and the Mo-S bonding is discussed.

Crystallization↗
PubMed1989

Structure of oxobis(phenolato)[tris(3,5-dimethyl-1-pyrazolyl)-hydroborato]molybdenum (V).

C27H32BMoN6O3, Mr = 595.34, monoclinic, P2(1)/n, a = 16.376 (6), b = 10.438 (5), c = 17.016 (8) A, beta = 107.25 (3) degrees, V = 2777.8 A3, Z = 4, Dm = 1.37, Dx = 1.43 g cm-3, Mo K alpha,lambda = 0.71073 A, mu = 5.02 cm-1, F(000) = 1228, T = 296 K, R = 0.038, wR = 0.045 for 2457 reflections. This molecule is the first structurally characterized mononuclear molybdenum complex containing a terminal aryl oxide ligand. The central molybdenum atom adopts a distorted octahedral coordination geometry with one face of the octahedron occupied by the tridentate pyrazolylborate ligand and the opposite face by the oxo and the two phenolato ligands. The structure is compared with that of the analogous benzenethiolate complex.

Borates↗
PubMed1989

Results for two children using a multiple-electrode intracochlear implant.

Assessments in speech perception, speech production, and language skills were conducted on two children, 5 and 10 years old at the time of surgery, using the Nucleus multiple-electrode cochlear implant. Data were collected pre- and post-operatively to measure changes in performance over time. For closed-set speech perception tests in the audition alone condition, post-operative performance was generally better than pre-operative performance and performance improved post-operatively for both patients. In closed-set vowel and consonant identification and open-set sentence perception for the older patient, post-operative improvements from the vision alone to the auditory-visual condition were recorded and performance improved post-operatively in both conditions. In all measures of speech production for both patients, post-operative scores were higher than pre-operative scores and performance improved post-operatively. In language skills, post-operative scores were higher than pre-operative scores and scores improved post-operatively in all measures for both patients.

Child↗