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Biomedical subjects

J English

Publications and source records attributed to J English.

At least 55 records · Page 3Linked to original sources
PubMed1996

Chalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T-DNA sequences.

Flower pigmentation patterns were scored in 185 sense Chalcone synthase (Chs) transgenotes and 85 antisense Chs transgenotes; upon first flowering, 139 (75%) of sense transgenotes were found to be phenotypically altered, as were 70 (82%) of the antisense transgenotes. The observed patterns document the range of phenotypic variations that occur, as well as confirm and extend the finding that sense Chs constructs produce several types of morphology-based flower pigmentation patterns that antisense Chs constructs do not. Long-term monitoring for epigenetic variations in one population of 44 sense Chs transgenotes showed that 43 (98%) were capable of producing a cosuppression phenotype. The primary determinant of sense-specific patterns of cosuppression of Chs was found to be the repetitiveness and organization pattern of the transgene, not 'position effects' by, or 'readthrough' from, flanking plant DNA sequences. The degree of cosuppression observed in progeny of transgenotes carrying multiple, dispersed copies as compared to that observed with a single copy of the transgene suggests that sense cosuppression of Chs is subject to a transgene dosage effect.

Acyltransferases↗
PubMed1996

A pilot study to evaluate paclitaxel (Taxol) as primary medical treatment for patients with inoperable stage III and IV breast carcinoma.

The activity of paclitaxel has been extensively investigated in previously treated patients with metastatic breast carcinoma. We evaluated the activity of paclitaxel as primary medical therapy in patients with stage III and IV breast carcinoma, 6 female patients were recruited with no previous history of surgery, radiotherapy or chemotherapy. Paclitaxel was administered as a 3-h infusion at a dose of 225 mg/m2 repeated every 3 weeks weekly to a maximum of 10 cycles. 2 patients achieved a complete response, one of whom had a normal trucut biopsy of the affected breast 6 months after discontinuation of chemotherapy and radiotherapy and a normal mammogram at 17 months. 3 patients achieved a partial response and one stabilised. The patients received between four and ten cycles of chemotherapy. Paclitaxel at this dose was associated with toxicity including alopecia, stomatitis, nausea and diarrhoea. Moderately severe neutropenia occurred in 4 patients, 2 requiring antibiotics but was of short duration and did not necessitate a dose reduction for subsequent courses. Paclitaxel has shown activity as primary medical therapy in patients with inoperable breast carcinoma at presentation at this dosage and schedule. One patient achieved a complete response and avoided surgery altogether and all 6 patients had their primary tumour downgraded. It may be indicated as a single agent in this context or in combination with other drugs with proven activity in breast carcinoma.

Adult↗
PubMed1996

Susceptibility to multiple cutaneous basal cell carcinomas: significant interactions between glutathione S-transferase GSTM1 genotypes, skin type and male gender.

The factors that determine development of single and multiple primary cutaneous basal cell carcinomas (BCCs) are unclear. We describe a case-control study firstly, to examine the influence of allelism at the glutathione S-transferase GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loci on susceptibility to these tumours and, secondly, to identify interactions between genotypes and relevant individual characteristics, such as skin type and gender. Frequency distributions for GSTM1 genotypes in cases and controls were not different, although the frequency of GSTM1 A/B was significantly lower (P = 0.048) in the multiple BCCs than in controls. We found no significant differences in the frequencies of GSTT1 and CYP2D6 genotypes in cases and controls. Interactions between genotypes were studied by comparing multinomial frequency distributions in mutually exclusive groups. These identified no differences between cases and controls for combinations of the putatively high risk GSTM1 null, GSTT1 null, CYP2D6 EM genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive genotypes were also not different. Frequency distributions of GSTM1 A/B with CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033). The proportion of males in the multiple BCC group (61.3%) was greater than in controls (47.0%) and single BCC (52.2%), and the frequency of the combination GSTM1 null/male gender was significantly greater in patients with multiple tumours (P = 0.002). Frequency distributions of GSTM1 null/skin type 1 were also significantly different (P = 0.029) and the proportion of subjects who were GSTM1 null with skin type 1 was greater (P = 0.009) in the multiple BCC group. We examined the data for interactions between GSTM1 null/skin type 1/male gender by comparing frequency distributions of these factors in the single and multiple BCC groups. The distributions were almost significantly different (exact P = 0.051). No significant interactions between GSTT1 null or CYP2D6 EM and skin type 1 were identified. Comparisons of frequency distributions of smoking with the GSTM1 null, GSTT1 null and CYP2D6 EM genotypes identified no differences between patients with single and multiple tumours.

Aged↗
PubMed1996

Hypogonadotrophic hypogonadism and primary amenorrhoea associated with increased melatonin secretion from a cystic pineal lesion.

A 17-year-old girl presented with primary amenorrhoea and failure to develop secondary sexual characteristics, although her height was above the 90th centile. Endocrine investigations revealed hypogonadotrophic hypogonadism (basal LH and FSH levels < 0.5 U/l; FSH rose to 2.0 U/l and LH to 1.0 U/l after GnRH). ACTH, GH, TSH and PRL secretion were normal. A magnetic resonance scan revealed no abnormality in the pituitary, pituitary stalk or hypothalamus but demonstrated a partly cystic enhancing lesion in the pineal region. Melatonin production (assessed as urinary 6-sulphatoxymelatonin: aMT6s) at baseline was markedly increased: 459-530 ng/kg/24 h compared with aged-matched controls: 136 +/- 69 (P = 0.01). However, melatonin production retained a largely normal rhythm with increased production during the night. Treatment with ethinyloestradiol 100 micrograms daily had no apparent effect on the production of melatonin. Treatment with atenolol, 100 mg daily at 1600 h, was associated with suppression of nocturnal melatonin secretion but a brisk rebound in the morning and a considerably delayed peak excretion time (10.2 h) compared with controls (3.9 h). It is likely the pineal lesion, which may be hyperplasia or possibly even tumour, was responsible for the increased melatonin secretion. These data support the hypothesis that melatonin may have a causal role in hypogonadotrophic hypogonadism.

Adolescent↗
PubMed1996

Melatonin regulation in humans with color vision deficiencies.

Light can induce an acute suppression and/or circadian phase shift of plasma melatonin levels in subjects with normal color vision. It is not known whether this photic suppression requires an integrated response from all photoreceptors or from a specialized subset of photoreceptors. To determine whether normal cone photoreceptor systems are necessary for light-induced melatonin suppression, we tested whether color vision-dificient human subjects experience light-induced melatonin suppression. In 1 study, 14 red-green color vision-deficient subjects and 7 normal controls were exposed to a 90-min, 200-lux, white light stimulus from 0200-0330 h. Melatonin suppression was observed in the controls (t = -7.04; P < 0.001), all color vision-deficient subjects (t = -4.76; P < 0.001), protanopic observers (t = -6.23; P < 0.005), and deuteranopic observers (t = -3.48; P < 0.05), with no significant difference in the magnitude of suppression between groups. In a second study, 6 red/green color vision-deficient males and 6 controls were exposed to a broad band green light stimulus (120 nm with lambda max 507 nm; mean +/- SEM, 305 +/- 10 lux) or darkness from 0030-0100 h. Hourly melatonin profiles (2000-1000 h) were not significantly different in onset, offset, or duration between the two groups. Melatonin suppression was also observed after exposure to the green light source at 0100 h (color vision deficient: t = -2.3; df = 5; P < 0.05; controls: t = -3.61; df = 5; P < 0.01) and 0115 h (color vision deficient: t = -2.74; df = 5; P < 0.05; controls: t = -3.57; df = 5; P < 0.01). These findings suggest that a normal trichromatic visual system is not necessary for light-mediated neuroendocrine regulation.

Adult↗
PubMed1996

Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight.

Serum levels of IGF-I and IGF-binding protein (IGFBP-1) have been determined in the maternal circulation between 11 and 42 weeks of gestation in women not in labour (n = 335) and in the maternal and fetal circulations at the time of delivery between 37 and 42 weeks (n = 55). Maternal serum (MS) IGF-I levels increased during pregnancy and showed a significant positive correlation with maternal weight (P = 0.0033) but no correlation with birthweight. The MS IGFBP-1 levels did not change during the second and third trimesters and showed a negative correlation with birthweight, maternal weight, placental weight and MS glucose (P = 0.0002, P < 0.0001, P = 0.047, P = 0.024 respectively). MS IGFBP-1 levels were higher in small-for-gestational age babies than in average-for-gestational weight babies (P = 0.026) and lower in the large-for-gestational weight group (P = 0.048). There was a significant rise in mean MS IGFBP-1 levels during labour (P = 0.0005). These findings suggest that IGFBP-1 may be an important factor in pathological growth retardation.

Birth Weight↗
PubMed1996

A struggle for equality: resistance to commissioning of male nurses in the Canadian military, 1952-1967.

Historical research was conducted to explore and describe the forces of resistance that prevented male registered nurses from being employed and conferred officer status in the Nursing Division of the Canadian military. Prior to 1967, only female nurses were permitted to join the Nursing Division. A 25-year struggle by the Registered Nurses Association of Ontario (RNAO), its Male Nurses Committee (MNC), and the Canadian Nurses Association (CNA) was required to change this discriminatory policy. The struggle for equality on behalf of Canadian male nurses was successfully resolved because of the united stand taken by the MNC, the RNAO, and the CNA. The study also demonstrates the need to move beyond matriarchal history perspectives in nursing to more completely understand the evolution of the profession in Canada.

Canada↗
PubMed1995

Idoxifene: report of a phase I study in patients with metastatic breast cancer.

Idoxifene, a novel antiestrogen with reduced estrogenic activity when compared to tamoxifen, has been given to 20 women with metastatic breast cancer, 19 of whom had received tamoxifen previously, in doses between 10-60 mg. Idoxifene had an initial half-life of 15 h and a terminal half-life of 23.3 days. At a maintenance dose of 20 mg, a mean steady-state level of 173.5 ng/ml was achieved. Significant falls in luteinizing hormone and follicle-stimulating hormone were seen, but the falls were not dose related. Idoxifene was well tolerated, with 11 patients complaining of mild symptoms similar to those seen with tamoxifen. Fourteen patients continued idoxifene therapy for 1-56 weeks; 4 patients showed stabilization of disease for 6-56 weeks and 2 patients showed a partial response.

Adult↗
PubMed1995

Initial culture behaviour of rat blastocysts on selected feeder cell lines.

To increase our understanding of rat embryos in culture and to attempt the isolation of blastocyst-derived cell lines, we examined the initial growth behaviour of rat blastocysts from four strains of rat on four different feeder cell layers. The feeders used were a continuous cell line of murine embryonic fibroblasts (STO), primary mouse (MEF) or primary rat (REF) embryonic fibroblasts, and a continuous cell line of rat uterine epithelial cells (RUCs). A medium that gave optimum plating efficiencies for murine ES cells was used in the rat embryo culture. Each culture system allowed hatching and attachment of the blastocysts, that is, the behaviour was similar on each feeder and each strain for the first 2 days in culture. Subsequently, there was a rapid differentiation of the Inner Cell Mass (ICM) cells on fibroblastic feeder cell layers (STO > MEF > REF), and this was generally complete after 3-6 days in primary culture. On RUCs, the ICM was found to increase in size without differentiation up to and including day 4 and in some cases longer. Embryo-derived cells were obtained by disaggregating and passaging ICMs on REF and RUC feeders. Rounded, refractile, and epithelial-like cells were isolated on REF and colonies of ES-like cells on the RUCs. The ES-like cells were positive for expression of alkaline phosphatase and stage-specific embryonic-antigen 1. This is an important first step towards the derivation and culture of pluripotent ES cells from the rat.

Alkaline Phosphatase↗
PubMed1995

Transfer of a mutated gene encoding active transforming growth factor-beta 1 suppresses mitogenesis and IL-1 response in the glomerulus.

Using in vivo gene transfer, we examined the anti-inflammatory potential of transforming growth factor-beta 1 (TGF-beta 1) in the renal glomerulus. TGF-beta 1 cDNA, modified to allow for secretion of the active form of TGF-beta 1, was introduced into cultured rat mesangial cells. The responses of the established transfectants were examined in culture. In vitro, the transduced mesangial cells showed a reduced mitogenic response to fetal calf serum and were insensitive to induction of matrix metalloproteinase-9 (MMP-9) by the proinflammatory cytokine IL-1 beta. To examine whether glomeruli which express active TGF-beta 1 in vivo are insensitive to these same stimuli, TGF-beta transfectants were transferred into normal rat glomeruli via renal artery injection. After 24 hours, isolated glomeruli containing transfectants exhibited TGF-beta bioactivity, a reduced mitogenic response, and repressed expression of MMP-9 in response to IL-1 beta. We further examined the responses of these chimeric glomeruli to an in vivo mitogenic stimulus by transferring TGF-beta transfectants into glomeruli of kidneys one day after the induction of anti-Thy-1 nephritis. The mitogenic activity of isolated glomeruli was examined four days after the cell injection. Compared to unmodified or mock cell-containing glomeruli, the in vivo mitogenic activity of glomeruli containing TGF-beta transfectants was significantly repressed. Furthermore, cellular outgrowth from nephritic glomeruli expressing active TGF-beta 1 was also suppressed ex vivo compared to controls. These data indicate that TGF-beta 1 inhibits mitogenesis and IL-1 response of the glomerulus and may, in part, act as a potential early suppressor of glomerular inflammation.

Animals↗
PubMed1995

Melatonin and adjustment to phase shift.

The pineal hormone melatonin has clear circadian phase-shifting effects in humans which have recently been formalized as a phase response curve. Its potential use in circadian rhythm disorders has been investigated in field studies of jet lag and shift work and in simulated phase shift. A substantial amount of information indicates that in the majority of subjects it hastens adaptation of both subjective and objective measures to forced shifts in time cues with few reported side-effects. Field studies of its use in adaptation to shift work are sparse and preliminary but the first indications are positive. In some blind subjects with sleep disturbance it can stabilize sleep onset time without necessarily entraining all circadian rhythms and it can advance sleep timing in delayed sleep-phase insomnia. Acute suppression of core body temperature may be an integral part of the phase-shifting mechanism.

Journal Article↗
PubMed1994

Acute phase-shifting effects of melatonin associated with suppression of core body temperature in humans.

Appropriately administered melatonin is able to phase shift circadian rhythms, to induce transient sleepiness and to suppress core body temperature. The relationships between these phenomena have not been fully explored. In a double-blind, placebo-controlled crossover study, 8 healthy males maintained a regular sleep-wake cycle in a natural environment throughout. From dusk until 2400 h on days (D) 1-4 subjects were in dim artificial lighting (< 100 lux) with darkness (< 1 lux) from 2400-0800 h. Sunglasses were worn during the day when outside. At 1700 h on D3 either melatonin (5 mg) or placebo was administered. Saliva samples were collected at 30 min intervals, 1600-2400 h on D3 and D4, and subjective alertness rated at 30 min intervals from 1600-2400 h on D3 and hourly from 0800-2400 h D4. Sleep quality was rated on nights 2, 3 and 4 and core temperature was recorded throughout. Melatonin induced a significant suppression of temperature and alertness peaking 2.5 h after the dose, together with improved sleep quality on the night of D3 and a phase advance of the endogenous melatonin rhythm on D4. The degree of phase shift was related to the amount of temperature suppression in 6 of 7 subjects with detectable melatonin, suggesting that temperature suppression is an integral part of the phase-shifting mechanism.

Adult↗
PubMed1994

A culture system for the development of the preimplantation rat embryo.

We describe a system for the culture of 1-cell rat embryos through to the blastocyst stage, using co-culture on specific feeder cell layers and particular defined media. We show that the use of rat uterine epithelial cells as a feeder layer, together with either M16M, CZB or HECM-1 media at 38.5 degrees C can improve the in vitro development of cultured rat embryos. There was considerable variation in the culture conditions, which were optimal for each strain of rat tested. We show that the 4 to 8-cell embryos are viable after reimplantation and that the second 4 to 8-cell block in the rat can be overcome using HECM-1 in a co-culture system, thus enabling the in vitro culture of rat embryos up to the blastocyst stage.

Journal Article↗
PubMed1993

A genetic analysis of DNA sequence requirements for Dissociation state I activity in tobacco.

Our objective was to test whether the double Ds structure correlated with Dissociation state I activity (i.e., high frequency of chromosome breakage and low frequency of reversion) in maize exhibited similar properties in tobacco. A genetic assay was established to test double Ds and related structures for their ability to cause loss of the linked marker genes streptomycin phosphotransferase and beta-glucuronidase in transgenic tobacco. An engineered double Ds element and a simple Ds element showed behavior consistent with that of state I and state II Ds elements, respectively, as described for maize. DNA structural rearrangements accompanied marker gene loss. Dissection of the double Ds structure showed that a left end and a right end of Ds in direct orientation were sufficient for the instability observed. This result suggested that left and right ends of Ds in direct orientation can participate in aberrant transposition events, consistent with two different models for double Ds-induced chromosome breakage proposed previously. Both models predict that the inversion of a half Ds element accompanies the aberrant transposition event. Such an inversion was detected by polymerase chain reaction experiments in tobacco and maize only when Activator activity was present in the genome.

Base Sequence↗