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Biomedical subjects

L M Williams

Publications and source records attributed to L M Williams.

At least 91 records · Page 5Linked to original sources

The ontogeny of central melatonin binding sites in the rat.

The maternal transfer of circadian rhythmicity and photoperiodic information to the fetus has been clearly demonstrated in several species, as has the importance of the pineal hormone, melatonin, in conveying this information. Maternal melatonin is known to readily cross the placenta and be taken up by the fetal brain. Specific melatonin receptors have been demonstrated in the rodent brain and pituitary from the 21st day of gestation. To better understand the mechanisms by which melatonin brings about the transfer of information to the fetus and to define the receptivity of the fetus to the melatonin signal, we have followed the ontogeny of central melatonin binding sites in the rat from the 13th day of gestation to 5 days after birth. The use of in vitro autoradiography allows for the precise localization of binding sites as well as their quantification. In the present study melatonin binding sites were first found on the 15th day of gestation, at which time specific binding was limited to the pituitary. At birth it was possible to identify a strong label in the pars tuberalis of the pituitary, whereas the pars distalis appeared to be less intensely and more unevenly labeled. Neuronal melatonin binding sites became apparent from day 17 of gestation in an area of the dorsal brain that in older fetuses and in neonatal rats appeared to be the paraventricular nucleus of the thalamus. Moreover, melatonin binding sites are identifiable over the suprachiasmatic nuclei from day 18 of gestation. These data show that the fetal pituitary may have the potential to respond to the maternal melatonin signal as early as the 15th day of gestation, and that the brain may attain that potential at the 17th or 18th day of gestation.

Animals↗

Characterization and autoradiographical localization of oxytocin receptors within the ovine endometrium in relation to post-partum corpus luteum function.

The induction of ovulation in early post-partum ewes is associated with a high incidence of premature luteal regression which is independent of the suckling stimulus but dependent on the stage post partum. The aim of the present study was to determine whether oxytocin receptors are present on uterine endometrium early in the luteal phase and hence ascertain whether oxytocin-induced uterine prostaglandin F2 alpha release is a possible mechanism involved in the premature regression of these post-partum corpora lutea. Ovarian and uterine tissues were collected on day 4 of the the cycle in ewes induced to ovulate at either 21 or 35 days post partum (n = 4 per group). A further four cyclic ewes were similarly synchronized to ovulate and acted as controls. Corpora lutea from the 21-day post-partum group were significantly (P less than 0.01) smaller, had a lower progesterone content and a reduced capacity to secrete progesterone in vitro than corpora lutea from 35-day post-partum or control ewes. A highly specific oxytocin receptor ligand 125I-labelled d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH29]-vasotocin was used to localize and characterize high affinity oxytocin receptors in uterine endometrium (dissociation constant 145 pmol/l). Oxytocin receptor concentrations in endometrium from ewes induced to ovulate at 21 days post partum were on average five-fold higher (P less than 0.05) than in 35-day post-partum and control groups.

Animals↗

Hemoperitoneum as a result of coital injury without associated vaginal injury.

Hemoperitoneum as a result of coital injury without associated vaginal injury is an extremely rare entity, and evidence by only five cases that have been reported in the medical literature to date. We report five additional cases encountered in two medical centers. Two of these were ruptured corpus luteum cysts, one was a laceration of the round ligament, another was a laceration of an ovary, and the fifth was rupture of a serous cystadenoma. This diagnosis should be considered in patients with hemoperitoneum after coitus.

Adult↗

Central melatonin receptors: implications for a mode of action.

The influence of melatonin on circadian and photoperiodic functions in numerous species is well documented. It is known that the effect of melatonin on circadian rhythmicity is mediated via the suprachiasmatic nucleus (SCN), the biological clock of the brain. It is not known however where the photoperiodic effects of melatonin are mediated. Evidence from brain lesioning and melatonin implant studies point to a site in or near the medial hypothalamus. In contrast to these studies, melatonin receptors have been reported in widespread areas of the brain, the pituitary and in peripheral tissues. The characteristics of the reported melatonin receptors vary widely between studies and consequently no definitive description of a physiologically relevant melatonin receptor has received universal recognition. This review marshals recent evidence for the localization and characterization of the melatonin receptor and discusses these findings in the context of the known effects of the hormone in different species.

Animals↗

Metallothionein immunoreactivity in the liver and kidney of copper injected rats.

Adult male rats were injected intraperitoneally with copper sulphate in physiological saline (3 mg copper/kg body wt). Metallothionein-I (MT-I) levels in liver, kidney, plasma and red blood cells were measured by radioimmunoassay (RIA), prior to the injection and after 7, 16 and 24 h. Copper and zinc levels in liver and kidneys were also monitored. Concentrations of MT-I in liver and kidneys showed a rapid increase and remained elevated for 24 h. Copper concentrations also increased in both tissues but zinc levels remained constant in the kidney and rose only slightly in the liver. MT-I levels increased gradually in plasma but decreased in the red blood cells. Immunochemistry of liver and kidney, using the direct peroxidase technique with antiserum to rat MT-I, revealed an increase in staining in both tissues after copper administration, consistent with the RIA results. The change in distribution of immunoreactive material with time after copper injection indicates a role for MT in the sequestration and excretion of copper in acutely loaded animals.

Animals↗

Neuropeptide Y (NPY) innervation of the ovine pineal gland.

A dense network of neuropeptide Y (NPY)-like immunoreactive (NPY-LI) fibres was revealed in the ovine pineal gland at the light microscope level. The dorsal and peripheral regions of the gland contained the most dense concentration of NPY-LI fibres with relatively few fibres in the mid-region and almost none in the pineal stalk. The effect of NPY in conjunction with isoproterenol (ISO) on cyclic AMP (cAMP) accumulation and noradrenaline (NA) on melatonin synthesis was investigated using in vitro techniques. NPY had no effect on the stimulation of cAMP or melatonin synthesis by the adrenergic agonists.

Animals↗

Advocacy for healthy births.

Each year, more than 250,000 American babies are born prematurely or with a low birthweight. Every two minutes a baby is born with a birth defect. These conditions cause and contribute to more than 40,000 infant deaths annually. Early and regular prenatal care is proven effective in reducing the risk of low birthweight. Given the importance of prenatal care, the March of Dimes advocates the availability of maternity care for all pregnant women. This article outlines the March of Dimes public affairs program, its involvement in the successful expansion of Medicaid coverage for poor pregnant women and infants, and the opportunity for continued advocacy to improve maternal and child health care.

Consumer Advocacy↗

Melatonin-binding sites in the rat brain and pituitary mapped by in-vitro autoradiography.

Using picomolar concentrations of [125I]iodomelatonin and in-vitro autoradiography, specific melatonin-binding sites have been mapped in the rat brain and pituitary. Using this same technique, high-affinity melatonin receptors had previously been identified in the suprachiasmatic nucleus (SCN) and median eminence regions of the rat hypothalamus. The presence of melatonin binding in the SCN has been confirmed, but the second area of binding has been identified as the pars tuberalis of the pituitary, and a completely novel area of binding is also reported in the area postrema. The existence of lower affinity melatonin receptors in the rat brain was also investigated using in-vitro autoradiography and higher concentrations of [125I]iodomelatonin. No further sites of specific binding were, however, disclosed.

Animals↗

Adrenergic and VIP stimulation of cyclic AMP accumulation in ovine pineals.

In vitro autoradiography of [125I]cyanopindolol ([125I]cyp) binding to sections of ovine pineal reveals a uniform distribution of beta-adrenergic receptors throughout the gland. Norepinephrine (NE) stimulated cyclic AMP production in pineal slices in both a time- and dose-dependent manner, producing a maximal two-fold increase. NE, isoproterenol (ISO) and epinephrine (E) stimulate cyclic AMP (cAMP) production with equal potency. NE stimulation of cAMP was totally blocked by propranolol (beta antagonist) but only partially blocked by practolol (a beta 1 preferential antagonist) indicating a mixed population of beta 1 and beta 2 receptor subtypes. Displacement of [125I]cyp binding by either practolol or zinterol (preferential beta 2 agonist) revealed IC50s of 1.3 x 10(-5) M and 9.95 x 10(-8) M respectively, confirming a mixed population of beta 1 and beta 2 receptors. A range of peptides previously localised within the pineal by immunocytochemistry were tested at a concentration of 10(-5) M for their effect on cyclic AMP production in pineal homogenates. Only vasoactive intestinal peptide (VIP) was effective showing a dose-dependent stimulation. ISO and VIP stimulation of cAMP were additive indicating action via independent receptors.

Animals↗

Autoradiographic studies of the renal clearance of circulating type I collagen fragments in the rat.

Cyanogen bromide (CNBr) peptides of [3H]-labelled type I collagen isolated from young rat skin were injected into adult rats via the tail vein. After 1, 5 and 10 minutes, the fate of the circulating radioactive peptides was investigated by measurement of the tissue distribution of radioactivity. Rapid removal of peptides from the circulation and their concomitant accumulation in the kidney proximal tubule epithelia was confirmed by autoradiography of kidney sections at the light microscope level. Immunopositive material was also identified and localized in proximal tubules using antibodies directed against denatured type I collagen chains and their CNBr degradation products. Ultrastructural autoradiography indicated that rapid removal of collagen peptides from the glomerular filtrate occurs via the brush border, apical vacuoles, and lysosomes.

Animals↗

Stimulation of melatonin synthesis in ovine pineals in vitro.

Static and superfused pineal slices (750 micron) have been used to study the control of melatonin synthesis by ovine pineals. Static incubates show a time-dependent accumulation of melatonin in the medium; this is significantly increased by stimulation with norepinephrine (NE) (10(-5) M), reaching 300% above control levels after 4 h. Perifused pineal slices show a rapid rise in melatonin release within 12-18 min in response to NE stimulation. This reaches a 3.5-4.5-fold increase in melatonin released within 30 min. Withdrawal of NE is associated with a rapid return to prestimulated levels within 12-18 min. These time-course characteristics compare favorably to those changes seen in vivo. The formation of [14C]melatonin from [14C]-tryptophan shows a linear increase with time. In the presence of NE (10(-5) M), the rate of synthesis is increased, albeit after an initial time lag of at least 30 min. The latter may reflect an N-acetyltransferase-independent mechanism of synthesis and release. In static incubations, propranolol (10(-5) M) inhibited NE-induced melatonin production by about 60%, but prazosin (10(-5) M) had no effect. As dibutyryl cyclic AMP (10(-3) M) stimulated melatonin production, it is concluded that beta-receptors are of primary importance to the control of melatonin production, as in the rat. The role of alpha 1-receptors is less clear, but the stimulatory action of phorbol 12-myristate 13-acetate on melatonin release implicates a receptor linked to phosphatidylinositol turnover.

Animals↗

Demonstration of melatonin-binding sites on the pars tuberalis of the rat.

Melatonin-binding sites have previously been identified in the suprachiasmatic nucleus (SCN) and median eminence (ME) of the rat. We have further investigated the localization of melatonin-binding sites in the rat hypothalamus and pituitary using the ligand [125I]iodomelatonin and in-vitro autoradiography. The presence of specific melatonin-binding sites in the SCN is confirmed; however the second area of melatonin binding is identified as the pars tuberalis of the pituitary and not the ME as previously described. No other areas which bound melatonin were found in either the pituitary or the hypothalamus.

Animals↗

Autoradiographic localization of beta-adrenergic receptors in the rabbit pituitary.

The localization and characterization of beta-adrenergic receptors in the rabbit pituitary have been studied using [125I]cyanopindolol as a specific ligand. Slide-mounted frozen sections were used for the autoradiographic localization and characterization of beta-adrenergic receptors. The displacement curves obtained from optical density of radioautograms or counting of scraped off sections demonstrated that beta-adrenergic receptors were mostly of the beta 2-subtype and highly concentrated in the intermediate lobe. Low concentrations of beta 2-adrenergic receptors were also found to be uniformly distributed in the anterior and posterior lobes. These results suggest that epinephrine and/or norepinephrine might play a physiological role in the regulation of the secretion of not only the intermediate lobe but also the anterior and posterior lobes of the rabbit pituitary.

Animals↗

Association of intracranial aneurysm and arteriovenous malformation.

In a series of 252 patients (47 with arteriovenous malformation, 205 with aneurysms), two patients had a coexisting intracranial aneurysm and an arteriovenous malformation. In one patient, the aneurysm was proximal to the main feeding arteries of the arteriovenous malformation. In the other patient, there was no anatomical relationship between the two lesions. These findings illustrate different views on the pathogenesis of the rare association of the two conditions.

Humans↗

Fluprostenol-induced softening of the cervix of the pregnant rat.

Fluprostenol, an analogue of prostaglandin F2 alpha, administered s.c. to rats on day 18 of pregnancy increased cervical creep, or softness, by the following day. Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions. Fluprostenol produced falls in serum progesterone concentrations, increases in 20 alpha-dihydroprogesterone concentrations, no changes in oestradiol or relaxin concentrations and a reduction in the ovarian human chorionic gonadotrophin binding capacity in vitro. Fluprostenol was less potent in inducing cervical softness when administered per vaginam, and a dose which produced softening in pregnant rats was ineffective in ovariectomized steroid-maintained pregnant or pro-oestrous rats. The findings suggest that cervical softening by fluprostenol does not result from a simple direct action on the cervix or by increasing uterine contractions, but rather by an indirect hormonal action mediated by the ovaries. The results with the lowest dose of fluprostenol indicate that cervical softening could be produced without a sustained fall in serum progesterone concentrations. Fluprostenol is much more potent at increasing cervical softness in the pregnant rat than prostaglandin F2 alpha or prostaglandin E2. With fluprostenol the ratio of dose to induce uterine contractility relative to that to produce cervical softness was greater than with these natural prostaglandins, indicating the greater selectivity of fluprostenol in the pregnant rat.

Animals↗