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Biomedical subjects

G H Watson

Publications and source records attributed to G H Watson.

At least 19 recordsLinked to original sources
PubMed1996

Effects of interferon-tau and progesterone on oestrogen-stimulated expression of receptors for oestrogen, progesterone and oxytocin in the endometrium of ovariectomized ewes.

The effects of recombinant ovine interferon-tau (IFN-tau) and progesterone on oestrogen-stimulated expression of endometrial receptors for oestrogen (ER), progesterone (PR) and oxytocin (OTR) were determined in ovariectomized ewes. Cyclic ewes (n = 16) were ovariectomized and fitted with uterine catheters on Day 4 of the oestrous cycle (Day O, oestrous) and assigned randomly in 2 x 2-factorial arrangement to receive daily intrauterine injections of either recombinant ovine IFN-tau (roIFN-tau; 2 x 10(7) anti-viral units) or control proteins from Day 11 to Day 15 and 50 mg progesterone from either Day 4 to Day 10 (E-P) or Day 4 to Day 15 (E+P). All ewes received 50 micrograms oestradiol-17 beta on Days 13, 14 and 15 and were hysterectomized on Day 16. In control ewes, endometrial ER mRNA, PR protein and OTR density were greater in E-P- than E+P- treated ewes. In E-P ewes, roIFN-tau decreased oestrogen-stimulated increases in ER and OTR, but not PR expression compared with control ewes. In E+P ewes, endometrial ER mRNA and protein, PR mRNA and protein, and OTR levels were lower in roIFN-tau-treated ewes than control ewes. Immunoreactive ER and PR were absent in the endometrial luminal and superficial glandular epithelium of roIFN-tau compared with control ewes, but were present in the deep glandular epithelium and stroma regardless of steroid or protein treatment. These results indicate that progesterone affects oestrogen-induced increases in endometrial ER, PR and OTR expression in the PR+ deep glandular epithelium and stroma, whereas IFN-tau suppresses oestrogen-induced increases ER, PR and OTR expression in the PR- luminal and superficial glandular epithelium. These combined actions of IFN-tau and progesterone to suppress oestrogen-induced increases in endometrial OTR formation would prevent pulsatile production of luteolytic prostaglandin F2 alpha by the endometrium during early pregnancy.

Animals↗
PubMed1996

Regional differences and up-regulation of progesterone receptors in adipose tissues from oestrogen-treated sheep.

Differing risk factors between men and women for a number of vascular and metabolic diseases have been linked to regional obesity. The differences in the distribution of adipose tissues between men (abdominal or upper-body obesity) and women (gluteal/femoral or lower body obesity) suggest a role for sex steroids in the regional distribution of fat. Previous work from this laboratory has shown the presence of oestrogen receptor (ER) in gluteal, perirenal and omental adipose tissues of ewes with similar physical characteristics to the ER in uterine tissue. The concentration profile for adipose ER was gluteal > perirenal > omental. In this report, we determined the physiological significance of adipose ERs by showing an up-regulation of the progesterone receptor (PR) in adipose tissues after oestrogen treatment in a fashion similar to that seen in a major responsive tissue such as uterus. Using PR antibodies (PR-6 and C-262), Western blot analysis of PR from oestrogen-treated sheep indicated that PR was induced in uterus >>> gluteal adipose > perirenal adipose consistent with the concentration of ER contained in these tissues. PR could not be detected by Western blotting in omental adipose tissue from oestrogen-treated animals or in gluteal, perirenal and omental adipose tissues from untreated animals. Sucrose gradient profiles of progestin (R-5020) binding from uterus and gluteal adipose tissues of oestrogen-treated ewes showed specific binding in both the 5S and 9S regions of the gradient, while perirenal and omental adipose tissue had only the 5S peak. The amount of specific binding was increased with oestrogen treatment in all the tissues. When gluteal adipose tissue cytosol was preincubated with PR antibody (C-262) to prevent binding of ligand and subjected to sucrose gradient analysis, both the 5S and 9S regions were diminished, suggesting that both peaks contained PR. Dilution of uterine cytosol resulted in an increase in the ratio of the 5S to the 9S peak, indicating that the 9S PR complex dissociates at low concentrations; this may be the reason why only the 5S peak was observed in perirenal and omental adipose tissues. These data offer further support for a direct role of sex steroids in regional adipose accretion and metabolism.

Adipose Tissue↗
PubMed1995

Intrauterine injection of ovine interferon-tau alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes.

This study determined the effects of intrauterine injections of recombinant ovine interferon-tau; (roIFN-tau; 2 x 10(7) antiviral units/day) or control proteins (6 mg/day) from day 11 to day 14 post-oestrus = day 0) on endometrial expression of receptors fro oestrogen, progesterone and oxytocin in cyclic ewes. Plasma concentrations of progesterone were greater on day 15 in ewes receiving roIFN-tau compared with control proteins (P < 0.02, treatment x day). Ewes injected with roIFN-tau had lower endometrial levels or oestrogen receptor mRNA (P > 0.10) and protein (P < 0.01) on day 15 compared with ewes receiving control proteins. In situ hybridization analysis indicated that oestrogen receptor mRNA was more abundant in the luminal and glandular epithelium of control ewes compared with roIFN-tau-treated ewes. Immunoreactive oestrogen receptor was also present in the luminal and glandular epithelium of control, but not roIFN-tau-treated ewes. Endometrial levels of progesterone receptor mRNA and protein were not different (P > 0.10) between control and roIFN-tau-treated ewes. In situ hybridization analyses indicated that progesterone receptor mRNA abundance was low in endometrial epithelium and stroma of both control and roIFN-tau-injected ewes. Immunoreactive progesterone receptors were present in the endometrial stroma and epithelium of control ewes, but confined to the stroma of roIFN-tau-treated ewes. Oxytocin receptor density was lower (P < 0.01) in the endometrium of ewes injected with roIFN-tau than control proteins; however, oxytocin receptor affinity was not affected (P > 0.10) by treatment. Concentrations of 13,14-dihydro-15-ketoprostaglandin F2a (PGFM) were not increased by exogenous oxytocin administration in control and roIFN-tau-treated ewes on days 10 or 12 post-oestrus. However, on day 14, control ewes responded to oxytocin with increased plasma concentrations of PGFM, whereas ewes receiving roIFN-tau remained unresponsive to oxytocin. These results indicate that the an tiluteolytic effects of IFN-tau are to prevent increases in endometrial oestrogen receptor MRNA and protein and oxytocin receptor density which abrogates uterine release of prostaglandin F2a during maternal recognition of pregnancy. IFN-tau may inhibit the synthesis of oestrogen receptor mRNA by a transcriptional or post-transcriptional regulatory mechanism to suppress oxytocin receptor formation during early pregnancy in ewes.

Analysis of Variance↗
PubMed1994

Immunocytochemical localization and changes in endometrial progestin receptor protein during the porcine oestrous cycle and early pregnancy.

Changes of progesterone receptor (PR) protein and cellular localization in the endometrium were evaluated during the oestrous cycle and early pregnancy of the gilt. During the oestrous cycle, the concentration of total PR protein within the endometrium was highest on Days 0-5 and decreased on Day 10. The endometrial concentration of PR reached a nadir on Day 12 and this level was maintained throughout the remainder of the oestrous cycle (Day 18). In pregnant gilts, the concentration of endometrial PR protein from Day 10 to Day 18 was similar to that in cyclic gilts. Western blot analysis with antiserum specific for the A and B isoforms of PR indicated that porcine endometrium expresses both isoforms of PR. Immunostaining was detectable for both the A and B isoforms of PR from Day 0 to Day 12 of the oestrous cycle. However, no staining was observed on Day 15 and Day 18 of the oestrous cycle or pregnancy Immunocytochemical localization of PR in the endometrium of cyclic gilts and pregnant gilts indicated that there was intense staining for PR in surface epithelium and glandular epithelium during oestrus (Day 0) and on Day 5. However, the staining was less intense on Day 7 and Day 10 of the oestrous cycle and no epithelial staining was observed after Day 12. PRs were present in the stroma and myometrium throughout the oestrous cycle and early pregnancy. The presence of conceptuses during pregnancy did not affect the loss of PR from the uterine epithelium after Day 10 of gestation. Down-regulation of epithelial PR might be one factor involved in the timing of luteolysis during the oestrous cycle as well as conceptus growth and placentation during early pregnancy.

Animals↗
PubMed1993

Biochemical and immunological characterization of oestrogen receptor in the cytosolic fraction of gluteal, omental and perirenal adipose tissues from sheep.

Determination of the presence and characterization of oestrogen receptors (ERs) in subcutaneous and internal fat depots were performed and compared with ERs in the uterus using ligand binding and immunological techniques. Successful and consistent measurement of ERs in ovine adipose tissue could only be accomplished in animals depleted of endogenous sex steroids by combined ovariectomy and adrenalectomy. Scatchard, sucrose gradient and Western blot analyses all confirmed the presence of ERs in the cytosolic fractions of various adipose and uterine tissues from ovariectomized-adrenalectomized ewes. The approximate Kd values of 0.1-0.4 nmol/l for oestradiol binding in cytosolic fractions of gluteal, omental and perirenal adipose tissues were similar to the expected high affinity binding of Kd 0.35 nmol/l observed in uterine tissue. The binding was specific for oestrogens, as unlabelled diethylstilboestrol and oestradiol effectively competed with labelled hormone for receptor sites and progesterone, R5020, testosterone and dexamethasone all failed to compete. Mean (+/- S.E.M.) concentrations of ERs, expressed as fmol specific binding sites per mg protein, were much lower (P < 0.05) in adipose tissues than in uterine tissue (975 +/- 33). However, the content of ERs was greater (P < 0.05) in subcutaneous gluteal fat (11.5 +/- 0.8) than in the internal omental or perirenal fat (5 +/- 0.6) depots. ERs from adipose and uterine tissues both migrated as moieties of 8S on 5-20% sucrose gradients. Western blot analysis of ERs from uterine and adipose tissues in the presence of protease inhibitors demonstrated an immunostaining band with a molecular mass of 67 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Cardiac rhabdomyomas in tuberous sclerosis.

Echocardiography was performed in 60 people with tuberous sclerosis (TSC) to ascertain the prevalence of cardiac rhabdomyomas at different ages. Twenty-five of 43 children, but only 3 of 17 adults, had tumors, the difference being highly significant. The number and absolute size of the tumors in those who had any were much the same throughout childhood, although the tumors in adults were smaller. Four cases of prenatal tumor recognition are also described; all four later showed signs of TSC, although none had tumors at birth. One of these four is already included in the series of 60, and one single tumor was removed surgically; in the other two the tumors regressed, as they did in the only three infants in the group of 60. The evidence presented herein, together with some published case reports, suggests that echocardiography may afford the most useful diagnostic test for TSC in early infancy and also that a conservative policy should be followed in the management of symptomatic tumors.

Adolescent↗
PubMed1991

Watson syndrome: is it a subtype of type 1 neurofibromatosis?

Over 20 years ago, Watson described three families with a condition characterised by pulmonary valvular stenosis, café au lait patches, and dull intelligence. Short stature is an additional feature of this autosomal dominant condition. A fourth family with Watson syndrome has since been reported. We have had the opportunity to review members of three of these four families. The clinical phenotype of Watson syndrome has been expanded to include relative macrocephaly and Lisch nodules in the majority of affected subjects, and neurofibromas in one-third of family members. Because the additional clinical findings enhance the similarity between Watson syndrome and neurofibromatosis 1, molecular linkage studies have been performed using probes flanking the NF1 gene on chromosome 17. Probe HHH202 showed the tightest linkage to Watson syndrome with a maximum lod score of 3.59 at phi = 0.0 (95% confidence limits of phi = 0.0-0.15). This suggests either that Watson syndrome and neurofibromatosis 1 are allelic, or that there is a series of contiguous genes for pulmonary stenosis, neurocutaneous anomalies, short stature, and mental retardation on 17q.

Chromosomes, Human, Pair 17↗
PubMed1990

Tuberous sclerosis presenting with fetal and neonatal cardiac tumours.

Cardiac tumours were identified on ultrasonography in fetal or early postnatal life in five infants. Tuberous sclerosis was subsequently diagnosed in all five. Only one infant required operation. Regression of the tumour occurred in three. No infant had hypomelanotic macules at birth, and they took up to two years to appear.

Adult↗
PubMed1989

Cardiac rhabdomyomata in tuberous sclerosis: their course and diagnostic value.

Echocardiography was performed in 60 people with tuberous sclerosis to ascertain the prevalence and course of cardiac rhabdomyomata at different ages. Twenty five (58%) of 43 children had tumours, but only three (18%) of 17 adults. The tumours tended to remain the same size through childhood. Only three infants were included but evidence from this and some published case reports suggest that the tumours tend to regress in early infancy and again in adolescence. The prevalence of tumours in young infants with tuberous sclerosis is likely to be considerably above 50%. As other signs of tuberous sclerosis are usually absent at this age echocardiography may afford the most useful diagnostic test in early infancy.

Adolescent↗
PubMed1988

Microsomal receptor for steroid hormones: functional implications for nuclear activity.

Target tissues for steroid hormones are responsive by virtue of and to the extent of their content of functional intracellular receptors. Recent years have seen a shift in considerations of the cellular dynamics and distribution of these receptors, with current views favoring predominant intranuclear localization in the intact cell. This paper summarizes our analyses of the microsomal estrogen and androgen binding capability of rat uterine and ventral prostate tissue, respectively; these studies have revealed a set of high affinity sites that may act as a conduit for estrogen traversing the cell en route to the nucleus. These sites have many properties in common with cytosolic receptors, with the salient difference of a failure to activate to a more avid DNA-binding form under conditions which permit such activation of cytosolic receptors. The microsomal estrogen-binding proteins also have appreciable affinity for progesterone, another distinction from other known cellular estrogen receptor species. Various experimental approaches were employed to demonstrate that the microsomal receptors were not simply cytosol contaminants; the most convincing evidence is the recent successful separation of the cytosolic and microsomal forms by differential ammonium sulfate precipitation. Discrete subfractionation of subcellular components on successive sucrose gradients, with simultaneous assessments of binding capability and marker enzyme concentrations, indicates that the major portion of the binding is localized within the vesicles of the endoplasmic reticulum free of significant plasma membrane contamination. The microsomal receptors are readily solubilized by extraction with high- or low-salt-containing buffers or with steroid. The residual microsomes following such extraction have the characteristics of saturable acceptor sites for cytosolic estrogen-receptor complexes. The extent to which these sites will accept the cytosolic complexes is equal to the concentration of microsomal binding sites extracted. These observations suggest three possible roles for the microsomal receptor-like proteins: (a) modulation of estrogen access to nuclear binding sites; (b) formation of functional complexes which diffuse to other extranuclear sites to alter non-genomic cellular processes; (c) regulation of nuclear concentration of estrogen-receptor complexes by virtue of producing microsomal acceptor sites for uptake of free or loosely associated nuclear complexes, previously thought to exist in the cytoplasm.

Animals↗
PubMed1986

Double connections in total anomalous pulmonary venous connection.

Three infants who underwent operation for total anomalous pulmonary venous connection had unobstructed drainage of all the pulmonary veins to both the coronary sinus and left vertical vein. In one patient the anatomy was demonstrated preoperatively and complete correction accomplished without difficulty, but in two patients the second connection was discovered only at postoperative reinvestigation. Arbitrary classification of total anomalous pulmonary venous connection into cardiac, supracardiac, infracardiac, and mixed types does not lend itself to description of such lesions and may obscure their clinical importance. For these less common variants of total anomalous pulmonary venous connection, a more detailed and precise definition of morphology facilitates accurate surgical repair.

Cardiac Catheterization↗
PubMed1985

Atresia of the coronary sinus orifice.

The cases of two children are reported in whom atresia of the right atrial orifice of the coronary sinus was diagnosed at cardiac catheterization. Only one previous case diagnosed in life has been found in the literature, though there are 34 necropsy reports. In nearly half the cases a persistent left superior vena cava has afforded the only outflow channel for the coronary sinus, and occasionally this may have surgical implications.

Child↗
PubMed1985

Velo-cardio-facial syndrome presenting as holoprosencephaly.

A baby with holoprosencephaly and the tetralogy of Fallot is described. The mother had operative correction of the same cardiac lesion and shows features typical of the velo-cardio-facial syndrome, an autosomal dominant disorder. The association between holoprosencephaly and this condition has not been previously reported. When holoprosencephaly is found associated with congenital heart disease, velo-cardio-facial syndrome should be sought in other family members.

Abnormalities, Multiple↗
PubMed1985

Specific binding of estrogen and estrogen-receptor complex by microsomes from estrogen-responsive tissues of the rat.

Rat uterine and anterior pituitary microsomes each contain a population of specific estrogen-binding sites. Saturation binding of estradiol is demonstrable, with an affinity similar to that of the cytosol estrogen receptor (Ka = 1-2 X 10(10) M-1). Dissociation rate kinetic determinations, however, revealed that estrogen-microsomal complexes are 4 times as stable as cytosol estrogen-receptor complexes. Sedimentation properties in sucrose gradients were salt-dependent, yielding values of 10S in KCl-free buffer and 5.5S in the presence of 0.4 M KCl. The concentration of microsomal sites varies in proportion to the level of cytosol estrogen receptor, such that microsomal binding constitutes a consistent 20% of the total extranuclear binding capacity. Binding is sensitive to pronase, but not to ribonuclease or deoxyribonuclease; steroidal specificity differs from cytosol receptor only with respect to a greater extent of competition by progesterone. Microsomal binding sites are readily extractable with KCl-free hypotonic buffer or with 0.4 M KCl, but are resistant to extraction by 0.15 M KCl. The presence of estradiol lends stability to the microsomal binding sites, while high salt has a deleterious effect on their longevity. After exhaustive extraction of binding sites, microsomes are capable of accepting cytosol estradiol-receptor complexes to a level corresponding to the concentration of depleted binding sites; microsomes from nontarget tissue do not manifest such capability. However, the original microsomal estrogen-binding sites are not simply cytosol receptor contaminants, as evidenced by the observations that the microsomal binding site concentration is independent of the volume of tissue homogenate (indicating that a trapping phenomenon is not operative) and that nonextracted microsomes are not potential acceptor sites for cytosol estradiol-receptor complexes. In considering total cellular dynamics of estrogen and estrogen receptor turnover, it thus becomes important to explore the role of the microsomal compartment, since it functions as a repository of specific estrogen-binding sites and may have significant acceptor capability for the cytosol estrogen-receptor complex.

Animals↗
PubMed1984

Consanguinity and complex cardiac anomalies with situs ambiguus.

A survey of British born Asian and English populations of children with congenital cardiac anomalies showed an increased incidence in the Muslim Asian population of complex lesions with visceral heterotaxia. There is a very high incidence of parental consanguinity among Muslim Asian children with complex congenital cardiac anomalies that is even higher than in the general Muslim Asian population of the area studied. The evidence suggests an important recessive genetic component in complex cardiac lesions with visceral heterotaxia, but segregation analysis does not support pure recessive inheritance.

Abnormalities, Multiple↗