PubMed Health⌕ Search

Biomedical subjects

H Watson

Publications and source records attributed to H Watson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Regulation of epidermal growth factor receptor synthesis by ovarian steroids in human endometrial cells in culture.

The aim of this study was to investigate the effect of oestradiol and progesterone on epidermal growth factor (EGF) binding in human endometrial glands and stromal cells in culture. Monolayers of isolated glands or stromal cells were cultured for 6 days in the presence or absence of steroids which were replenished daily. Binding of 125I-labelled EGF was measured in the presence and absence of unlabelled EGF. Over a 6 day period, oestradiol caused a dose-dependent increase in the number of EGF receptors in stromal cells, with a maximum effect of 150% control at a concentration of 10 nmol l-1. The effect of progesterone was also dose dependent and reached a maximum of 170% control at 100 nmol progesterone l-1. Oestradiol and progesterone in combination caused a greater increase in EGF receptor concentration than did either steroid alone (control, 100 +/- 11%; oestradiol, 144 +/- 11% control; progesterone, 200 +/- 20% control; oestradiol and progesterone, 288 +/- 6% control). Steroid treatment did not alter the affinity of the receptor for EGF. The stage of the cycle of the tissue did not affect the response to steroids. The effect of oestradiol was inhibited by the anti-oestrogen ICI182780, and that of progesterone by the anti-progestin RU486. In endometrial glands, neither oestradiol nor progesterone affected the number of EGF receptors, but the two steroids in combination induced an increase of 140 +/- 23% control where control was 100 +/- 15%. These data demonstrate that oestradiol and progesterone increase the number of EGF receptors in vitro, and suggest that EGF is involved in mediating the actions of these steroids on the processes of proliferation and differentiation in the human endometrium.

Cell Culture Techniques↗
PubMed1995

Purification, crystallisation and preliminary X-ray analysis of the vanadium-dependent haloperoxidase from Corallina officinalis.

The vanadium-dependent haloperoxidase from the seaweed Corallina officinalis has been purified to homogeneity and crystallised. The protein is reported to be a hexamer of 12 x 64,000 Da, contains no haem, and is dependent on vanadium for activity. The crystals are grown from polyethylene glycol (PEG) 6,000 and 0.4 M potassium chloride. They are stable and diffract to better than 2 A resolution. They are of a cubic space group I23 (or 12(1)3) with cell dimensions a = b = c = 310 A.

Crystallization↗
PubMed1994

The epidermal growth factor receptor in the human endometrial adenocarcinoma cell line HEC-1-B.

The binding characteristics and steroidal regulation of the EGF receptor were investigated in the human endometrial adenocarcinoma cell line HEC-1-B. The cell line was shown to possess a single, high affinity binding site for epidermal growth factor receptor (EGF) with a Kd of 3.09 +/- 1.39 nM (mean +/- SD, n = 6) and binding of 845 +/- 311 fmol/mg protein (mean +/- SD, n = 6). The protein kinase C activator, phorbol 12-myristate, 13-acetate (PMA) increased the Kd of the EGF receptor in a dose dependent manner (PMA: 0, 1, 10, 100 nM; Kd: 4.1, 5, 10, 50 nM, respectively). The effect of PMA (10 nM) was overcome by preincubating the cells with the protein kinase C inhibitor staurosporine (1 microM) prior to the addition of PMA. The effect of the ovarian steroids oestradiol and progresterone on EGF receptor accumulation was studied by pretreating the cells for 6 days with oestradiol or progesterone in phenol red free DMEM:F12, 1:1 supplemented with 5% charcoal stripped fetal calf serum. Both steroids were shown to increase EGF receptor number with a maximum 5- and 7-fold increase in the presence of 1 nM oestradiol or 1 microM progresterone, respectively. The study demonstrates the presence of a high affinity binding site for EGF in HEC-1-B cells which is regulated by oestradiol and progresterone.

Adenocarcinoma↗
PubMed1994

Public health medicine training and the NHS changes.

The current round of mergers between Health Authorities and Family Health Service Authorities (FHSAs), when set in the competitive context of markets, has profound implications for training in Public Health Medicine. This paper considers the phases in the management of change and the costs, benefits and principles for trainers, trainees and organisations as mergers take place. Particular emphasis is placed on understanding the motives of and learning from the change that is taking place.

Health Facility Merger↗
PubMed1994

An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases.

A total of 500 consecutive women (mean age 32.9 years; SD 5 years) presenting with a history of recurrent miscarriages (median 4; range 3-17) were investigated for the presence of antiphospholipid antibodies (APA), polycystic ovaries (PCO), hypersecretion of luteinizing hormone (LH) and chromosome abnormalities in order to detect an underlying cause of their pregnancy losses. All women had details of their previous reproductive history, investigations and treatment documented: 76% of the women had experienced only early pregnancy losses (miscarriage < 13 weeks gestation); 32% had a history of subfertility; and significant parental chromosome rearrangements were present in 3.6% of couples. An ultrasound diagnosis of PCO was made in 56% of women, 58% of whom were demonstrated to hypersecrete LH, based on early morning urinary LH analysis. Circulating APA were found in 14% of women. An underlying cause of recurrent miscarriage--genetic, endocrine or autoimmune--was found in > 50% of couples. Women in the latter two groups are being recruited to randomized treatment trials which are discussed.

Abortion, Habitual↗
PubMed1994

Characterization of epidermal growth factor receptor in human endometrial cells in culture.

The aim of the study was to determine the binding characteristics of the epidermal growth factor (EGF) receptor in isolated human endometrial glands and stromal cells in culture. Stromal cells and glands were obtained from endometrial tissue by collagenase dispersion followed by sieve filtration. They were plated into 24-well multiwell plates in Ham's F10 medium supplemented with 5% fetal calf serum and used at 70-80% confluence. Scatchard analysis revealed a single class of high-affinity binding sites in both cell types with apparent dissociation constants of 1.17 +/- 0.6 (n = 15) and 1.20 +/- 0.3 (n = 8) nmol 1-1 for stromal cells and glands, respectively. The concentration of receptors was higher in stromal cells than in glands, 719 +/- 377 (n = 16) and 310 +/- 177 (n = 8) fmol mg-1 protein, respectively. Epidermal growth factor labelled with 125I was displaced from the receptor by EGF and transforming growth factor alpha, but not insulin, insulin-like growth factor, fibroblast growth factor, or platelet-derived growth factor. Binding was shown to be dependent on time and temperature. Downregulation of the receptor was demonstrated by preincubating cells with 5 nmol EGF I-1, which reduced receptor concentrations by 75%. 12-O-Tetradecanoylphorbol-13-acetate decreased the affinity of the receptor for EGF changing the dissociation constant from 1.8 to 3.9 nmol l-1. A suitable system for investigating the regulation of this receptor in human endometrium was established.

Cells, Cultured↗
PubMed1993

Rotary subluxation of the scaphoid: a spectrum of instability.

Rotary subluxation of the scaphoid is not an "all or nothing" phenomenon, but a spectrum of instability including constant displacement of the scaphoid apparent on plain non-stress radiographs (the previously defined static type), subluxation seen only on loading X-rays or other special studies ("dynamic"), and instability demonstrable on physical examination but not by radiographic studies ("predynamic"). A clinical study of 1,000 random individuals was carried out to determine the incidence of unilateral hypermobility of the scaphoid. 21% of the subjects were found to have an abnormal difference in mobility between their scaphoids. The incidence of significant symptoms and physical findings associated with this hypermobility was determined.

Adult↗
PubMed1993

Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.

Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels.

Abortion, Habitual↗
PubMed1993

Albumin synthesis rates in cirrhosis: correlation with Child-Turcotte classification.

Albumin-synthesis rates were measured in nine patients with stable cirrhosis and compared with those of eight healthy volunteers by means of a new technique using stable isotopes. Four grams of L-[1-13C]leucine was injected over 10 min, and blood samples were drawn at intervals. Serum free [13C]leucine enrichment, taken to be the precursor for albumin synthesis, and 13C enrichment of leucine in albumin, isolated with differential solubility in absolute ethanol from trichloracetic acid-precipitated serum proteins, were measured on mass spectrometry. Albumin synthesis, expressed as a fractional rate, was 7.9% +/- 0.3%/day in the controls and 7.9% +/- 1.1%/day in the cirrhotic patients. Albumin synthesis, expressed as an absolute rate, was lower in the cirrhotic group (cirrhotic, 119 +/- 17 mg/kg/day; controls, 146 +/- 8 mg/kg/day), but because of the relatively small number of patients the difference was not significant. However, the absolute rate of albumin synthesis significantly correlated with the Child-Turcotte score (p = 0.024) and its Pugh modification (p = 0.027). The rate of albumin synthesis also correlated with serum phenylalanine concentration but not with serum albumin concentration and intravascular albumin mass or with other clinical indexes of liver function or integrity when taken separately. However, the significant correlation between albumin synthesis and Child score suggests that albumin synthesis might be useful for the clinical judgment of patients with cirrhosis.

Humans↗
PubMed1992

Elevation of albumin synthesis rates in nephrotic patients measured with [1-13C]leucine.

Eight patients with a nephrotic syndrome and a histologically-proven kidney disease were compared to age- and sex-matched healthy volunteers. Albumin synthesis rates were measured after injection of 13C-labelled leucine (57 mg/kg body wt, 19.4 atoms%). Plasma volume was determined with 125I-albumin. The fractional synthesis rate of albumin was 7.9 +/- 0.4%/day in control subjects in comparison with a marked elevation to 18.4 +/- 2.0%/day (P less than 0.001) in nephrotic patients. The absolute synthesis rate was 145 +/- 9 mg/kg/day in control subjects compared with 213 +/- 17 mg/kg/day (P = 0.005) in the nephrotic patients. There was a statistically significant correlation between ASR and urinary albumin loss (P = 0.035) and serum cholesterol concentration (P = 0.007). The calculated oncotic pressure was significantly lower in the nephrotic group than in the controls (P less than 0.001), but was without correlation with ASR.

Adult↗
PubMed1992

Endometrial phospholipases A2, polycystic ovaries and pelvic pain.

OBJECTIVE: To compare the activity of calcium independent phospholipase A2 in the endometrium of women with polycystic ovaries and in women with normal ovaries, and to investigate the influence of chronic pelvic pain on phospholipase A2 activity. DESIGN: A prospective descriptive study. SETTING: The Samaritan Hospital for Women and the Unit of Metabolic Medicine, St Mary's Hospital Medical School, London. SUBJECTS: 73 women attending the Samaritan Hospital for Women for clip sterilization, infertility, early recurrent miscarriage or pelvic venous congestion. 45 of these women had no pelvic pain, 22 had normal ovaries and 23 had polycystic ovaries diagnosed by ultrasound. The other 28 women had chronic pelvic pain, 14 of them had normal ovaries and 14 polycystic ovaries. INTERVENTIONS: Endometrial tissue was obtained at curettage or from the excised uterus in the proliferative or secretory phase of the menstrual cycle. The activities of calcium dependent (type 1) and calcium independent (type 2) phospholipase A2 isoenzymes were measured in all endometrial samples. RESULTS: In all the women phospholipase A2 type 1 activity, was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). There was no difference between women with normal ovaries and those with polycystic ovaries at either stage of the cycle irrespective of whether or not chronic pelvic venous congestion was present. In women with normal ovaries, both with and without chronic pelvic pain, phospholipase A2 type 2 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.02 and P less than 0.05 respectively) but in women with polycystic ovaries, with and without chronic pelvic pain, there was no significant difference in activity between the two phases of the cycle. Women with polycystic ovaries had markedly higher proliferative phase type 2 activity than women with normal ovaries (P less than 0.001). Secretory phase type 2 activity was similar in all the women investigated. CONCLUSION: These data suggest that phospholipase A2 type 2 activity is increased in proliferative phase endometrium of women with polycystic ovaries but that the increase is not associated with chronic pelvic venous congestion.

Arachidonic Acid↗
PubMed1992

Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin.

OBJECTIVE: To assess the effect of moderate obesity on the outcome of induction of ovulation with low dose gonadotrophin in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective analysis of women with PCOS treated consecutively. An analysis of the impact of obesity on outcome of pregnancy using data from the North West Thames Regional (NWTR) obstetric database was included for comparison. SETTING: Induction of ovulation clinic at the Samaritan Hospital for Women (St. Mary's Hospital Group). SUBJECTS: 100 women with clomiphene-resistant anovulation associated with PCOS. 75 were of normal weight (BMI 19-24.9 kg/m2, lean group) and 25 were moderately overweight (BMI 25-27.9 kg/m2, obese group). INTERVENTIONS: Induction of ovulation using low doses of gonadotrophins with small, stepwise increments in dosage as required. MAIN OUTCOME MEASURES: Rates of ovulation, pregnancy and miscarriage; daily and total doses of gonadotrophin required for induction of ovulation. RESULTS: The proportion of ovulatory cycles was significantly greater in the lean group (77%) compared with the obese group (57%) (chi 2 9.8, P less than 0.001). Obese women required larger doses of gonadotrophin to achieve ovulation (P less than 0.001). The proportion of women who achieved at least one pregnancy was similar in the two groups (39% vs 48%) but miscarriage was more frequent in the obese group (60% vs 27%; P less than 0.05). This difference was independent of the baseline and/or mid-follicular luteinizing hormone (LH) concentration either before or during treatment. Analysis of data from the North West Thames Health Region obstetric database confirmed an increased risk of miscarriage in moderately obese women which was independent of maternal age. CONCLUSIONS: Moderate obesity in women with PCOS, treated with low dose gonadotrophin, is associated with an increased risk of miscarriage. This is reflected in the results of analysis of the effect of obesity on outcome of pregnancy in the general population. It is therefore important to encourage weight reduction in obese women with PCOS before considering therapy to induce ovulation.

Abortion, Spontaneous↗
PubMed1991

Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort.

Markers of immune function present before infection may determine the subsequent course of disease in HIV-infected individuals. In 1983, we measured immune function in a group of haemophiliacs in Edinburgh. In 1984, 18 of these patients became infected with HIV-1 from contaminated factor VIII. We have followed-up these patients since their seroconversion. The rate of disease progression, as assessed by the appearance or not of AIDS symptoms or signs within five years of seroconversion, was related both to the concentration of total plasma IgM before exposure to infection and to the pattern of specific IgM and IgA anti-HIV response around the time of IgG seroconversion. Disease progression also correlated with concentrations of plasma interleukin-2 receptor (a marker of lymphocyte activation) and with the number and percentage of circulating DR + ve (activated) T cells. Our findings show that the extent of host immune reactivity, which may be genetically determined, is a powerful factor in the pathogenesis of HIV-associated disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Low-dose gonadotrophin therapy for induction of ovulation in 100 women with polycystic ovary syndrome.

Women with anovulation due to polycystic ovary syndrome are likely to develop multiple follicles during gonadotrophin therapy and therefore have a high risk of multiple pregnancy. We have developed a low-dose regimen for use in these women; 100 women with clomiphene-resistant polycystic ovary syndrome were treated. Ninety-five of the women ovulated at least once, 72% of the 401 cycles induced were ovulatory and the majority (73%) of these were uni-ovulatory. The overall cumulative conception rate was 55% at 6 months with only two multiple pregnancies. The rate of early pregnancy loss was 32%, which is similar to that reported by other groups. The prevalence of complications was low with no cases of severe hyperstimulation and less than 5% of cycles were abandoned because of development of multiple follicles. Analysis of baseline and mid-follicular luteinizing hormone levels showed that a raised baseline and/or mid-follicular luteinizing hormone level was associated with a poor response to treatment, i.e. anovulation, ovulation but no conception, or early pregnancy loss. There were no successful pregnancies in the women whose luteinizing hormone levels were persistently raised during ovulatory cycles. Low-dose gonadotrophin therapy is a safe and effective method of inducing ovulation; it is associated with a high incidence of single follicular development and a very low multiple pregnancy rate.

Clomiphene↗
PubMed1991

Phospholipase activity in the endometrium of women with normal menstrual blood loss and women with proven ovulatory menorrhagia.

The activity of phospholipase A2 types 1 and 2 and phospholipase C was measured in the endometrium of women with ovulatory menorrhagia and in those with normal menstrual blood loss. In both groups of subjects phospholipase A2 type 1 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). The median activity (pmol/mg protein/min) for the proliferative phase was 27.6 in normal subjects and 40.4 in women with ovulatory menorrhagia and for the secretory phase the median activity was 144.5 in normal women and 138.1 in women with ovulatory menorrhagia. There was no difference between the two groups of women at either stage of the cycle. Phospholipase A2 type 2 activity was also higher in the secretory phase than in the proliferative phase (P less than 0.05 for normal subjects and P less than 0.001 for women with menorrhagia). The median activity (pmol/mg protein/min) for the proliferative phase was 94.4 (normal subjects) and 56.6 (women with menorrhagia) and for the secretory phase 148.3 (normal subjects) and 142.5 (women with menorrhagia). The activity of phospholipase A2 type 2 was significantly lower in the proliferative phase of women with ovulatory menorrhagia compared with normal subjects (P less than 0.05). Phospholipase C activity (nmol/mg protein/min) was significantly higher in women with ovulatory menorrhagia (median 8.2) compared with women with normal blood loss (median 5.5) (P less than 0.01).

Endometrium↗
PubMed1989

HIV-related risk behaviour among a non-clinic sample of injecting drug users.

This paper focuses upon HIV-related risk behaviour among a sample of injecting drug users purchasing injecting equipment at a retail pharmacy in Glasgow. It is shown that the majority of the individuals interviewed were concerned about HIV/AIDS and that many were optimistic about their chances of avoiding contracting the virus. However, it is shown that the shared use of injecting equipment was continuing and that many individuals were prepared to provide their own injecting equipment to others, even if they were unprepared to re-use it again themselves. We also consider here the possibility of encouraging drug injectors to switch to non-injecting drug use and the potential basis for any sexual transmission between drug injectors and others. The paper concludes with a consideration of some of the policy implications of this work.

Adolescent↗