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Biomedical subjects

M A Webster

Publications and source records attributed to M A Webster.

At least 37 records · Page 2Linked to original sources
PubMed1995

Continuous combined piperazine oestrone sulphate and medroxyprogesterone acetate hormone replacement therapy--a study of bleeding pattern, endometrial response, serum lipid and bone density changes.

This pilot study was conducted to establish the optimum oral dosage of medroxyprogesterone acetate (Provera) given daily in combination with a fixed dose of piperazine oestrone sulphate (Ogen), as hormone replacement therapy. A group of 32 nonhysterectomized, symptomatic menopausal women were randomly allocated to receive piperazine oestrone sulphate 1.25 mg daily and medroxyprogesterone acetate 2.5 mg, 5 mg or 10 mg daily for a 2-year period. This was an open study and the patients were reviewed at 3-monthly intervals for 2 years. Vaginal bleeding was reported by 58% of patients after the first 3 months of treatment. There was a gradual decline in the reported incidence of bleeding over the following 6 months particularly by women in the 5 mg and 10 mg Provera group. Only 10% of patients were still recording slight bleeding in the 10 mg group at 12 months. By 24 months all the women in the 5 mg and 10 mg Provera groups had ceased bleeding. There were 2 patients in the 2.5 mg Provera group with persistent proliferative endometrium at 24 months. All the remaining patients had atrophic endometrium. There was no significant difference in serum lipid changes between the 3 groups, but there was an overall reduction in total cholesterol, triglycerides and low density lipoprotein cholesterol in all women. There was no significant difference in bone mineral density changes between the groups over the 2-year period. Endometrial protection with increased incidence of amenorrhoea, without significant adverse effects, was seen with the use of 5 mg and 10 mg of provera.

Administration, Oral↗
PubMed1994

The influence of contrast adaptation on color appearance.

Most models of color vision assume that signals from the three classes of cone receptor are recoded into only three independent post-receptoral channels: one that encodes luminance and two that encode color. Stimuli that are equated for their effects on two of the channels should be discriminable only to the remaining channel, and are thus assumed to isolate the responses of single channels. We used an asymmetric matching task to examine whether such models can account for changes in color appearance following adaptation to contrast--to temporal variations in luminance and chromaticity around a fixed mean luminance and chromaticity. The experiments extend to suprathreshold color appearance the threshold adaptation paradigm of Krauskopf, Williams and Heeley [(1982) Vision Research, 32, 1123-1131]. Adaptation changes the perceived color of chromatic test stimuli both by reducing their saturation (contrast) and by changing their hue (direction within the equiluminant plane). The saturation losses are largest for test stimuli that lie along the chromatic axis defining the adapting modulation, while the hue changes are rotations away from the adapting direction and toward an orthogonal direction within the S and L-M plane. Similar selective changes in both perceived color and perceived lightness occur following adaptation to stimuli that covary in luminance and chromaticity. The selectivity of the aftereffects for multiple directions within color-luminance space is inconsistent with sensitivity changes in only three independent channels. These aftereffects suggest instead that color appearance depends on channels that can be selectively tuned to any color-luminance direction, and that there are no directions that invariably isolate responses in only a single channel. We use the perceived color changes to examine the spectral sensitivities of the chromatic channels and to estimate the distribution of channels. We also examine how adaptation alters the contrast-response function, how it affects reaction times for luminance and chromatic contrast, the extent to which the aftereffects exhibit interocular transfer, and the way in which the perceived color changes differ from those induced by conventional light adaptation.

Adaptation, Ocular↗
PubMed1994

Mammary tumors expressing the neu proto-oncogene possess elevated c-Src tyrosine kinase activity.

Amplification and overexpression of the neu (c-erbB2) proto-oncogene has been implicated in the pathogenesis of 20 to 30% of human breast cancers. Although the activation of Neu receptor tyrosine kinase appears to be a pivotal step during mammary tumorigenesis, the mechanism by which Neu signals cell proliferation is unclear. Molecules bearing a domain shared by the c-Src proto-oncogene (Src homology 2) are thought to be involved in signal transduction from activated receptor tyrosine kinases such as Neu. To test whether c-Src was implicated in Neu-mediated signal transduction, we measured the activity of the c-Src tyrosine kinase in tissue extracts from either mammary tumors or adjacent mammary epithelium derived from transgenic mice expressing a mouse mammary tumor virus promoter/enhancer/unactivated neu fusion gene. The Neu-induced mammary tumors possessed six- to eightfold-higher c-Src kinase activity than the adjacent epithelium. The increase in c-Src tyrosine kinase activity was not due to an increase in the levels of c-Src but rather was a result of the elevation of its specific activity. Moreover, activation of c-Src was correlated with its ability to complex tyrosine-phosphorylated Neu both in vitro and in vivo. Together, these observations suggest that activation of the c-Src tyrosine kinase during mammary tumorigenesis may occur through a direct interaction with activated Neu.

Animals↗
PubMed1994

Mammary tumorigenesis and metastasis in transgenic mice.

The transgenic mouse has emerged as an important model system to assess the transforming potential of oncogenes in the mammary epithelium. Mammary gland-specific expression of oncogenes in transgenic mice has resulted in the induction of a variety of phenotypes ranging from benign epithelial hyperplasias to metastatic mammary tumors. The induction of tumors in most of these transgenic models is a multi-step process where transgene expression, although required, is not sufficient for conversion of the primary mammary epithelial cell to the transformed phenotype. While the identity of many of these collaborating genetic events is obscure, several approaches have been applied with might shed light on their nature. In a few exceptional transgenic strains, tumor progression can occur very rapidly suggesting that, if additional genetic events are required, they occur very frequently. Recent genetic and biochemical characterization of these strains offers insight into the molecular mechanisms that may underlie the complex phenotypic features exhibited by these transgenic strains.

Animals↗
PubMed1993

Contrast adaptation dissociates different measures of luminous efficiency.

We compared how contrast adaptation influences three alternative measures of luminous efficiency. Subjects judged the lightness, the flicker, or the motion of chromatic sine-wave gratings. Adaptation to gratings with correlated luminance and chromatic contrast strongly biases lightness matches and moderately biases minimum-motion settings for gratings that are counterphased at 1 Hz, but it has little effect on motion or flicker settings for gratings that are counterphased at 15 Hz. These results suggest that different measures of equiluminance tap neural pathways that can have different spectral sensitivities. At low temporal frequencies both perceived lightness and minimum-motion settings appear to depend on channels that do not represent luminance and color independently.

Adaptation, Ocular↗
PubMed1992

Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease.

Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have been implicated in the development of aggressive human breast cancer. To directly assess the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying unactivated neu under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were established. By contrast to the rapid tumor progression observed in several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the mammary epithelium resulted in the development of focal mammary tumors after long latency. The majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and protein. Overexpression of neu in the mammary tumors was also associated with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. These observations suggest that overexpression of the unactivated neu protein can induce metastatic disease after long latency.

Animals↗
PubMed1992

Reanalysis of lambda max variations in the Stiles-Burch 10 degrees color-matching functions.

Individual differences in the color matches made by normal observers can be attributed in part to small interobserver variations in the spectral peaks (lambda max) of the cone sensitivities. I compared two different analyses of these lambda max variations that were both based on the Stiles-Burch 10 degrees color-matching functions [Opt. Acta 6, 1 (1959)]: one that suggested that the lambda max values for individual cone classes fall into discrete subgroups [J. Neitz and G. H. Jacobs, in Colour Vision Deficiencies IX, B. Drum and G. Verriest, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1989)] and one that failed to find discrete clustering [J. Opt. Soc. Am. A 5, 1722 (1988)]. I conclude that there is not strong evidence for discrete lambda max variations in the Stiles-Burch matches.

Color Perception↗
PubMed1991

Changes in colour appearance following post-receptoral adaptation.

Current models of colour vision assume that colour is represented by activity in three independent post-receptoral channels: two encoding chromatic information and one encoding luminance. An important feature of these models is that variations in certain directions in colour space modulate the response of only one of the channels. We have tested whether such models can predict how colour appearance is altered by adaptation-induced changes in post-receptoral sensitivity. In contrast to the changes predicted by three independent channels, colour appearance is always distorted away from the direction in colour space to which the observer has adapted. This suggests that at the level at which the adaptation effects occur, there is no colour direction that invariably isolates only a single post-receptoral channel.

Adaptation, Physiological↗
PubMed1990

Obstetric risks and outcomes: birth centre compared with conventional labour ward.

Birth centres in Australia provide an option for women and their professional advisors when choosing the setting for childbirth. It is important that empirical information about the risks is available to enable informed decisions to be made. The purpose of this study was to compare the obstetric outcomes for women admitted to the Birth Centre at Royal Hospital for Women in Sydney with outcomes for women admitted to the conventional labour ward, controlling for prenatal and intrapartum risk. The findings indicate that, with the existing back-up provided by the conventional service, the outcomes for women admitted to the Birth Centre were at least as good as those of the other women. The study also shows that there are differences between the two settings in the management of the intrapartum period. The rate of intervention is substantially higher for women admitted to the Labour Ward, after risk is taken into consideration. The evaluation indicates that the Birth Centre offers a viable choice for women with relatively low obstetric risk.

Delivery Rooms↗
PubMed1990

Orientation and spatial-frequency discrimination for luminance and chromatic gratings.

We have examined the accuracy of orientation and spatial-frequency discrimination for sine-wave gratings that vary in either luminance or color. The equiluminant chromatic gratings were modulated along either a tritanopic confusion axis (so that they were detectable on the basis of activity in only the short-wavelength-sensitive cones) or an axis of constant short-wavelength-sensitive cone excitation (so that they could be detected on the basis of opposing activity in only the long- and medium-wavelength-sensitive cones). Grating contrasts ranged from the detection threshold to the highest levels that we could produce; the contrasts of the luminance and color patterns were equated for equal multiples of their respective detection thresholds. Discrimination thresholds for all patterns showed a similar dependence on stimulus contrast, rising sharply at low contrasts and becoming nearly asymptotic at moderate contrasts. However, even at threshold contrasts, observers could still reliably discriminate sufficiently large differences in the orientation or spatial frequency of all patterns, and they could also reliably identify the type of variation (luminance or which color) defining the grafting. For most conditions the discrimination thresholds did not differ from the two types of color grafting and reached values as low as 1 deg (orientation) or 4% (spatial frequency). Thus observers were able to make accurate spatial judgments on the basis of either type of chromatic information. However, these thresholds were slightly but consistently higher than the thresholds for comparable luminance graftings. This difference in the color and luminance discrimination thresholds may reflect somewhat coarser orientation and spatial-frequency selectivity in the mechanisms encoding the chromatic patterns.

Color Perception↗
PubMed1989

Induction of abortion in early first trimester human pregnancy using epostane.

The role of epostane (Sterling Winthrop, Guildford, UK), a competitive inhibitor of the 3 beta hydroxysteroid dehydrogenase enzyme system (3 beta-HSD), as an abortifacient agent in early human pregnancy has been studied in 54 women. All were less than 49 days from their last menstrual period. Thirty were treated with 200 mg of epostane every 8 h for 7 days and 24 were given 200 mg every 6 h for 7 days. This caused a sustained reduction in circulating progesterone concentrations, a smaller fall in 17 beta-oestradiol and no effect on serum cortisol. Abortion occurred in 21 women (70%) in the lower dosage group and in 20 women (87%) in the higher dosage group. Abortion was incomplete in 6 of these 41 women. A worsening of pregnancy nausea and vomiting was noted by 66% of women in the first group and 84% in the second. There was no delay in the resumption of normal menstruation following abortion. This study confirms the potential of epostane as an effective inhibitor of ovarian and placental steroidogenesis and as a potent abortifacient agent in early human pregnancy.

Abortifacient Agents↗
PubMed1988

Obstetric high risk screening and prediction of neonatal morbidity.

A retrospective study using an obstetric risk score protocol was applied to a stratified sequential sample of 843 singleton livebirths, occurring in the Royal Hospital for Women, Sydney, over a 12-month period (March, 1985-February, 1986). Data collection included 53 prenatal factors, 41 intrapartum factors and 37 neonatal factors. The study was comprised of 346 women admitted to the hospital birth centre and 497 women admitted to labour ward. In labour ward admitted women there was a significant association between high prenatal scores, high intrapartum scores and high neonatal morbidity scores. Women admitted to the birth centre were subjected to a screening procedure which resulted in low prenatal and relatively low intrapartum risk scores. However, neonatal morbidity scores were similar for both groups. The risk scoring protocol used in this study requires further revision to allow the adequate selection of low risk women delivering infants with a low risk of neonatal morbidity in a low risk obstetric setting.

Australia↗
PubMed1988

Factors underlying individual differences in the color matches of normal observers.

We have used a factor analysis of the Stiles-Burch [Opt. Acta 6, 1 (1959)] 10 degrees field color matches to examine the basis of individual differences in the color matches made by observers with normal color vision. The differences in the matches are primarily due to interobserver variations in the macular-pigment density [with a standard deviation (sigma) of 0.12 at 460 nm]; the lens-pigment density (sigma = 0.18 at 400 nm); the spectral position of the long-wavelength-sensitive (sigma = 50.3 cm-1), medium-wavelength sensitive (sigma = 31.9 cm-1), and short-wavelength-sensitive (sigma = 45.3 cm-1) photopigments; the covarying densities of the three photopigments (sigma = 0.045); and the degree of rod intrusion. Variations in the different factors appear to be uncorrelated. Comparable estimates of the sources and range of interobserver differences in color matching were obtained from a similar analysis of the Stiles-Burch 2 degrees color matches [Opt. Acta 2, 168 (1955)].

Color Perception↗
PubMed1988

Direct psychophysical estimates of the cone-pigment absorption spectra.

The absorption spectra of the long- and medium-wavelength-sensitive cone photopigments were derived by determining the spectra that best accounted for either the individual differences in the Stiles-Burch 10 degrees color matches [Opt. Acta 6, 1 (1959)] or the changes in color matches at high light levels due to photopigment bleaching [Vision Res. 20, 23 (1980)]. The estimates were made by finding the best-fitting coefficients for an 11th-order polynomial function of wavelength, with no requirement that the resulting sensitivities be consistent with the color-matching functions. The estimates are independent of the scaling effects of any inert screening filters and therefore directly reflect the photopigment sensitivities. The spectra implied by the differences in the matches are similar to the absorption spectra of Smith et al. [Vision Res. 16, 1087 (1976)], which were used as initial estimates. However, the peak sensitivity of the required long-wavelength-sensitive pigment is shifted toward slightly longer wavelengths.

Color Perception↗
PubMed1986

Temporal properties of brightness and color induction.

With a matching procedure, we studied the temporal properties of direct brightness (or lightness) and chromatic changes (produced by modulation of the region being matched) and induced brightness and chromatic changes (produced by modulation of the surround of the region being matched). The amount of direct brightness and color change was found to vary only slightly with temporal frequency over the 0.5-8 Hz range studied, whereas induced changes were found to occur only at low temporal frequencies, below about 2.5 Hz. With high temporal-frequency modulation of the surround, the induced patterns appeared to flicker but not to change in brightness or color. Despite the fact that chrominance and luminance temporal contrast sensitivity functions are very different, the temporal induction curves for color and brightness were very similar. However, brightness induction was found to increase approximately linearly with increasing surround modulation up to very high levels, whereas the amount of color induction was much less dependent on the modulation depth of the surround.

Color Perception↗
PubMed1985

Myometrial activity in first trimester human pregnancy after Epostane therapy. Effect of intravenous oxytocin.

The effect on myometrial activity of Epostane, a competitive inhibitor of the 3 beta-hydroxy steroid dehydrogenase enzyme system (3 beta-HSD) has been studied in 20 women awaiting termination of pregnancy. The women were randomly allocated by a double-blind procedure into two groups. In the Epostane-treated group there were significant falls in serum progesterone and oestradiol concentrations after 3 days of treatment. The placebo-treated group showed a small but significant decline in serum progesterone concentration. Insertion of an intrauterine balloon catheter for pressure measurements produced significantly greater uterine activity in the Epostane-treated group. The oxytocin response was variable and there was no significant difference between the two groups. A small rise in the peripheral plasma concentration of a prostaglandin F2 alpha metabolite (PGFM) was observed in the placebo group following oxytocin injection. There was a significant inverse correlation between post treatment progesterone values and uterine activity. Epostane appears to sensitize the myometrium to endogenous oxytocics and this probably results from progesterone 'withdrawal'. This effect may prove useful in potentiating the action of exogenous myometrial stimulants, such as prostaglandins, and may have a role in the termination of early pregnancy.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Interruption of first trimester human pregnancy following Epostane therapy. Effect of prostaglandin E2 pessaries.

The effect of Epostane, a competitive inhibitor of the 3 beta hydroxy steroid dehydrogenase enzyme system in combination with prostaglandin E2 (PGE2) for induction of abortion in early first trimester pregnancy has been studied in a group of 20 women awaiting termination of pregnancy. The women were consecutively assigned to four treatment groups. The first group was treated with PGE2 alone, administered vaginally as a lipid based (Witepsol) pessary. The remaining three groups received Epostane at differing doses for 5 days, and were treated with PGE2 on the fourth day. Significant falls in serum progesterone and oestradiol occurred in the Epostane-treated patients. Abortion was induced in one of the five control patients and in three of 10 patients treated with low doses (300-400 mg) of Epostane. Intrauterine pressure monitoring showed an increased reactivity to PGE2 in the treated groups. At the highest dose (600 mg) of Epostane, serum progesterone and oestradiol showed the greatest decline to 8% and 21% of the pretreatment values, a prompt and sustained pressure response occurred to PGE2 and abortion was induced in all five patients. A critical degree of progesterone suppression appears to sensitize the myometrium to exogenous prostaglandin. This combined treatment is an effective method of early pregnancy termination and may have a role in the management of mid-trimester abortion.

3-Hydroxysteroid Dehydrogenases↗